Ignite Creation Date:
2025-12-24 @ 4:36 PM
Ignite Modification Date:
2026-03-02 @ 3:43 PM
Study NCT ID:
NCT00938366
Status:
COMPLETED
Last Update Posted:
2016-04-14
First Post:
2009-07-09
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}], 'ancestors': [{'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017338', 'term': 'Cladribine'}, {'id': 'D000077402', 'term': 'Pantoprazole'}], 'ancestors': [{'id': 'D015762', 'term': '2-Chloroadenosine'}, {'id': 'D000241', 'term': 'Adenosine'}, {'id': 'D011684', 'term': 'Purine Nucleosides'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003839', 'term': 'Deoxyadenosines'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D012263', 'term': 'Ribonucleosides'}, {'id': 'D053799', 'term': '2-Pyridinylmethylsulfinylbenzimidazoles'}, {'id': 'D013454', 'term': 'Sulfoxides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D001562', 'term': 'Benzimidazoles'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'service@merckgroup.com', 'phone': '+49-6151-72-5200', 'title': 'Merck KGaA Communication Center', 'organization': 'Merck Serono, a division of Merck KGaA'}, 'certainAgreement': {'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Up to 1 year', 'eventGroups': [{'id': 'EG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.', 'otherNumAtRisk': 18, 'otherNumAffected': 2, 'seriousNumAtRisk': 18, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.', 'otherNumAtRisk': 17, 'otherNumAffected': 0, 'seriousNumAtRisk': 17, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Abdominal distension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA Version 10.1'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 17, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA Version 10.1'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Maximum Plasma Concentration (Cmax) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '20.7', 'spread': '28.2', 'groupId': 'OG000'}, {'value': '20.3', 'spread': '46.0', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The maximum or peak plasma concentration observed after the administration of cladribine.', 'unitOfMeasure': 'nanogram/milliliter', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'SECONDARY', 'title': 'Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '71.5', 'spread': '28.0', 'groupId': 'OG000'}, {'value': '71.3', 'spread': '36.6', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).', 'unitOfMeasure': 'hour*nanogram/milliliter', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '74.6', 'spread': '27.7', 'groupId': 'OG000'}, {'value': '75.0', 'spread': '34.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.', 'unitOfMeasure': 'hour*nanogram/milliliter', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'SECONDARY', 'title': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.5', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '1.0'}, {'value': '0.6', 'groupId': 'OG001', 'lowerLimit': '0.5', 'upperLimit': '1.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The tmax was defined as time taken by the drug cladribine to reach Cmax.', 'unitOfMeasure': 'hour', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'SECONDARY', 'title': 'Apparent Terminal Half-life (t1/2) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.0', 'spread': '18.2', 'groupId': 'OG000'}, {'value': '14.9', 'spread': '23.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The apparent terminal half-life was defined as the time required for the plasma concentration of drug cladribine to decrease 50 percent (%) in the final stage of its elimination.', 'unitOfMeasure': 'hour', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'SECONDARY', 'title': 'Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '134.0', 'spread': '27.7', 'groupId': 'OG000'}, {'value': '133.3', 'spread': '34.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'Clearance of a drug was a measure of the rate at which cladribine is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.', 'unitOfMeasure': 'liter/hour', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Cladribine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'categories': [{'measurements': [{'value': '2709', 'spread': '32', 'groupId': 'OG000'}, {'value': '2875', 'spread': '46', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.', 'unitOfMeasure': 'liter', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.'}, {'type': 'SECONDARY', 'title': 'Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Cladribine', 'description': 'Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.'}, {'id': 'OG001', 'title': 'Cladribine + Pantoprazole', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.'}], 'classes': [{'title': 'TEAEs', 'categories': [{'measurements': [{'value': '11.1', 'groupId': 'OG000'}, {'value': '0.0', 'groupId': 'OG001'}]}]}, {'title': 'SAEs', 'categories': [{'measurements': [{'value': '0.0', 'groupId': 'OG000'}, {'value': '0.0', 'groupId': 'OG001'}]}]}, {'title': 'AEs Leading to Death', 'categories': [{'measurements': [{'value': '0.0', 'groupId': 'OG000'}, {'value': '0.0', 'groupId': 'OG001'}]}]}, {'title': 'AEs Leading to Discontinuation', 'categories': [{'measurements': [{'value': '0.0', 'groupId': 'OG000'}, {'value': '0.0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 1 year', 'description': 'An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 1 year, that were absent before treatment or that worsened relative to pre treatment state. AEs Leading to Death and AEs Leading to Discontinuation were also presented in the outcome measure.', 'unitOfMeasure': 'percentage of subjects', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety analysis set included all the randomized subjects who received treatment with at least one dose of either cladribine or pantoprazole during the study period.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Cladribine Followed by Cladribine + Pantoprazole', 'description': 'Subjects received a single 10 milligram (mg) cladribine dose orally on Day 1 followed by a wash out period of 10-25 days. Subjects then received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post pantoprazole dose on second day. After administration of cladribine, subjects were required to fast for an additional 2 hours.'}, {'id': 'FG001', 'title': 'Cladribine + Pantoprazole Followed by Cladribine', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After a wash out period of 10-25 days, subjects received a single 10 mg cladribine dose orally.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'This was a crossover study.18 subjects were included and washout of 10 to 25 days separated each treatment period. Overall 17 subjects completed the trial.1 subject withdrew consent after completion of the first period (cladribine alone) and was excluded from Pharmacokinetic population.18 subjects were included in safety population.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '9', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Cladribine Followed by Cladribine + Pantoprazole', 'description': 'Subjects received a single 10 milligram (mg) cladribine dose orally on Day 1 followed by a wash out period of 10-25 days. Subjects then received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After administration of cladribine, subjects were required to fast for an additional 2 hours.'}, {'id': 'BG001', 'title': 'Cladribine + Pantoprazole Followed by Cladribine', 'description': 'Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After a wash out period of 10-25 days, subjects received a single 10 mg cladribine dose orally.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '44.56', 'spread': '11.75', 'groupId': 'BG000'}, {'value': '46.89', 'spread': '8.31', 'groupId': 'BG001'}, {'value': '45.72', 'spread': '9.95', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Baseline analysis population included all randomized subjects.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-03', 'completionDateStruct': {'date': '2009-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-03-15', 'studyFirstSubmitDate': '2009-07-09', 'resultsFirstSubmitDate': '2015-09-21', 'studyFirstSubmitQcDate': '2009-07-10', 'lastUpdatePostDateStruct': {'date': '2016-04-14', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2015-09-21', 'studyFirstPostDateStruct': {'date': '2009-07-13', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-10-20', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.'}], 'primaryOutcomes': [{'measure': 'Maximum Plasma Concentration (Cmax) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The maximum or peak plasma concentration observed after the administration of cladribine.'}, {'measure': 'Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.'}], 'secondaryOutcomes': [{'measure': 'Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).'}, {'measure': 'Time to Reach the Maximum Plasma Concentration (Tmax) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The tmax was defined as time taken by the drug cladribine to reach Cmax.'}, {'measure': 'Apparent Terminal Half-life (t1/2) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'The apparent terminal half-life was defined as the time required for the plasma concentration of drug cladribine to decrease 50 percent (%) in the final stage of its elimination.'}, {'measure': 'Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of Cladribine', 'timeFrame': 'Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose', 'description': 'Clearance of a drug was a measure of the rate at which cladribine is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.'}, {'measure': 'Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation', 'timeFrame': 'Up to 1 year', 'description': 'An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 1 year, that were absent before treatment or that worsened relative to pre treatment state. AEs Leading to Death and AEs Leading to Discontinuation were also presented in the outcome measure.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Multiple Sclerosis']}, 'descriptionModule': {'briefSummary': 'The purpose of the study is to assess the influence of pantoprazole on the pharmacokinetic profile of cladribine, especially in terms of extent of absorption of cladribine since pH-modifying drug may potentially affect the stability of cladribine and thereby its bioavailability'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Subjects with a body mass index less than or equal to (\\<=) 28 and have a body weight greater than (\\>) 60 kilogram (kg) and less than (\\<) 120 kg, at screening\n* Able to understand informed consent and had given written, informed consent\n* Had a diagnosis of clinically stable and definite multiple sclerosis (MS) by either McDonald or Poser criteria\n* Expanded disability status scale (EDSS) score not to exceed 5.0\n* Male or non-pregnant, non-breast feeding women aged 18 to 65 years, inclusive at the time that informed consent was obtained\n* Female subjects lacking childbearing potential defined as post-menopausal for at least two years, surgically or medically sterile or sexually inactive; or willing to avoid pregnancy by using an adequate method of birth control for 28 days prior to, during and up to 90 days after the last administration of trial medication\n\nOther protocol defined inclusion criteria could apply.\n\nExclusion Criteria:\n\n* Subjects presenting a severe or unstable disorder: poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, a significant pre-existing hematological disease, or any medical condition, which in the opinion of the investigator, would constitute a risk or a contraindication for the participation of the subject to the study or that could interfere with the study objectives, conduct or evaluation\n* Subjects who were on MS treatment; and subjects who were on a non-stable symptomatic MS treatment (stable dose was defined as 3 weeks or longer prior to first study dose)\n* Clinically significant abnormal laboratory test results or electrocardiogram findings that in the opinion of the investigator could increase the safety risk to the subject\n* Positive results from serology examination for Hepatitis B surface antigen (HbsAg) not due to vaccination, hepatitis B core antibody (HbcAb), Hepatitis C virus antibody (anti-HCV) or Human Immunodeficiency antibody (anti-HIV)\n* Signs and symptoms of Transmissible Spongiform Encephalopathy at screening, or family members who suffered from such\n* Presence of chronic or recurrent infection or any acute infection within the last 2 weeks before first dosing in each study period\n* Presence of gastrointestinal disease that, in the opinion of the investigator, could affect the pharmacokinetic outcome of the study\n* Consumption of any concomitant medication that could directly influence gastric acidity (example: use of antacids, histamine receptor (H2) antagonists or other proton pump inhibitor) taken within 7 days of study day 1 and throughout the study period\n* Intake of alcoholic beverages, caffeine and caffeine containing beverages, grapefruit, oranges, cranberries and juices of these three fruits or smoking in the 48 hours prior to first dose and 48 hours post dose (cladribine)\n* Exposure to any investigational drug or the use of any investigational device in the 12 weeks prior to first dose\n* Intake of any medications that could directly influence gastrointestinal motility and absorption of cladribine (example, use of H2-antagonists, proton pump inhibitors) 7 days prior to cladribine administration\n* Any immunomodulatory therapy (including but not limited to glatiramer acetate, interferons, or natalizumab) and treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days of first dosing\n* Any cytokine or anti-cytokine therapy, IV immunoglobulin administration or plasmapheresis was prohibited in the 3 months prior to first dosing\n* Current history or presence of drug or alcohol abuse, confirmed by positive test results for drugs of abuse and/or alcohol or had a history of drug or alcohol abuse. Alcohol abuse was defined as: an average daily intake of more than 3 units or a weekly intake of more than 21 for males and 14 units for females where 1 unit equals 8-10 gram alcohol (1 unit equals 340 milliliter \\[mL\\] of beer, 115 mL of wine or 43 mL of spirits)\n* History or presence of hypertension or other significant cardiovascular abnormality, history of heart or kidney disease\n* Current diagnosis or personal history of cancer\n* Smoke 10 cigarettes or more per day or equivalent\n* Loss or donation of more than 400 mL of blood in the 12 weeks prior to first dose.\n* Definite or suspected personal history or family history of adverse drug reaction or hypersensitivity to drugs with a similar chemical structure to cladribine or pantoprazole or with known hypersensitivity to cladribine or pantoprazole excipients\n* Presence or history of any serious allergy (requiring hospitalization or prolonged systemic treatment)\n* Pregnant or nursing women. Treatment of pregnant and nursing women with cladribine in this study was prohibited\n* Signs or symptoms of neurological disease other than MS that could explain the symptoms of the subject'}, 'identificationModule': {'nctId': 'NCT00938366', 'briefTitle': 'Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck KGaA, Darmstadt, Germany'}, 'officialTitle': 'An Open-label, Cross Over Study, to Assess the Interactions of Pantoprazole (Proton Pump Inhibitor) With Oral Cladribine Administered in Subjects With Multiple Sclerosis', 'orgStudyIdInfo': {'id': '27967'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cladribine followed by Cladribine + Pantoprazole', 'description': 'Subjects will receive a single dose of cladribine10 milligram (mg) orally on Day 1. After a wash out period of 10-25 days, subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose.', 'interventionNames': ['Drug: Cladribine', 'Drug: Pantoprazole']}, {'type': 'EXPERIMENTAL', 'label': 'Cladribine + pantoprazole followed by Cladribine', 'description': 'Subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose. After a wash out period of 10-25 days, subjects will receive a single dose of cladribine 10 mg orally.', 'interventionNames': ['Drug: Cladribine', 'Drug: Pantoprazole']}], 'interventions': [{'name': 'Cladribine', 'type': 'DRUG', 'description': 'Subjects will receive two single doses of 10 mg cladribine orally in either first or second intervention period followed by a washout period of 10-25 days.', 'armGroupLabels': ['Cladribine + pantoprazole followed by Cladribine', 'Cladribine followed by Cladribine + Pantoprazole']}, {'name': 'Pantoprazole', 'type': 'DRUG', 'description': 'Subjects will receive a pantoprazole 40 mg orally for 2 consecutive days either in first or second intervention period.', 'armGroupLabels': ['Cladribine + pantoprazole followed by Cladribine', 'Cladribine followed by Cladribine + Pantoprazole']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Medical Responsible, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Merck Serono S.A. - Geneva, an affiliate of MerckKGaA, Darmstadt, Germany'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck KGaA, Darmstadt, Germany', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Merck Serono S.A., Geneva', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}