Ignite Creation Date:
2024-05-05 @ 12:04 PM
Last Modification Date:
2024-10-26 @ 9:20 AM
Study NCT ID:
NCT00235729
Status:
COMPLETED
Last Update Posted:
2009-03-20
First Post:
2005-10-06
Brief Title:
Lofexidine for Inpatient Opiate Detox
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 1024 - A Phase III Randomized Multi-Center Double Blind Placebo-Controlled Study of Safety and Efficacy of Lofexidine for Relief of Symptoms in Subjects Undergoing Inpatient Opiate Detoxification
Status:
COMPLETED
Status Verified Date:
2009-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The main objective of this study is to investigate the effectiveness of lofexidine in reducing withdrawal symptoms among subjects undergoing opiate detoxification Currently lofexidine is the most commonly used non-opiate medication for detoxification from opiates in the United Kingdom UK There is no non-opiate medication approved by the Food and Drug Administration FDA for the same indication in the United States US The only medications currently approved by the FDA for opiate detoxification are methadone and buprenorphine These medications however have the potential to be abused Lofexidine on the other hand offers a unique advantage for opiate detoxification because it is not addicting is easy to use and has a favorable safety profile
Detailed Description:
Primary Objective The primary objective of this study is to investigate the efficacy of lofexidine hydrochloride an alpha-2-adrenergic agonist in reducing withdrawal symptoms in subjects undergoing opioid detoxification as assessed by 1Day 3 SOWS-Gossop score during treatment phase and 2Time to dropout during treatment phase
Secondary Objectives Secondary objectives include determining Lofexidines 1 Efficacy in the reduction in withdrawal symptoms in subjects undergoing opioid detoxification assessed by longitudinal changes in SOWS-Gossop OOWS-Handelsman VAS-E and MGCI subject and rater 2Efficacy in the reduction in the need of any concomitant medication to alleviate opiate withdrawal symptoms 3 Efficacy in increasing the number of completers during the treatment phase and 4 Safety in the study population
Study Design This is a randomized multi-center double blind placebo-controlled parallel-group study There are 3 major phases of the study During Phase I Screening screening assessments will be performed during Phase II Days 1-5 subjects will be admitted to an inpatient unit and randomized to receive either lofexidine 08 mg QID or placebo QID after the baseline assessments are performed prior to randomization on Day 1 and during Phase III Days 6-8 all subjects will receive placebo QID on Days 6-7 and then be discharged on Day 8 following the post-treatment assessments An adaptive randomization procedure will be used to randomly allocate subjects in one of the two treatment groups - lofexidine or placebo
Study Population 264 subjects with Diagnostic and Statistical Manual for Mental Disorders Fourth Edition DSM-IV criteria for current dependence on any opioid with a half-life similar to heroin or morphine determined by structured clinical interview SCID will be randomized in one of the treatment groups 132 subjects per group Subjects at least 18 years-of-age with positive urine toxicology screen for opiates and negative for methadone LAMLAAM or buprenorphine during screening with the ability to understand and provide written informed consent that meet all the inclusion criteria and do not meet any of the exclusion criteria may be randomized into the study
Treatments On Day 1 subjects are randomized to either lofexidine or placebo and receive lofexidine 08 mg 4 x 02 mg lofexidine tablets QID or placebo 4 matching placebo tablets QID Lofexidine or placebo will be administered orally within 15 minutes before or after 0800 1300 1800 and 2300 hours on Days 1-5 On Days 6 and 7 all subjects will receive placebo using the same dosing schedule as above
Efficacy Assessments The primary efficacy outcome measures will be the Short Opiate Withdrawal Scale SOWS-Gossop scores range 0-30 on Day 3 of the treatment phase defined as Days 1-5 and the number of days representing the duration of stay in the treatment program after randomization SOWS-Gossop will be administered once during Baseline on Day 1 prior to randomization and after 35 hours after the first dose on Days 1 - 7 Secondary outcome measures evaluating the treatment effects on opioid withdrawal symptoms include the proportion of subjects requiring any concomitant medication to alleviate opiate withdrawal symptoms and the proportion of subjects who are completers In addition the composite longitudinal scores of the SOWS-Gossop Objective Opiate Withdrawal Scale OOWS-Handelsman Modified Global Clinical Impression Scale Subject and Rater and Visual Analog Scale - Efficacy VAS-E will also be used to assess the treatment efficacy to reduce the withdrawal symptoms OOWS-Handelsman MGCI Subject and Rater and VAS-E will be administered once during Baseline on Day 1 prior to randomization and 35 hours after the first dose on Days 1-7
Safety Assessments After signing the informed consent and completing the consent quiz the subject will complete Screening assessments to determine eligibility for study enrollment A complete physical examination will be performed on the first day of screening A repeat physical exam will be performed at 3-4 hours after randomization on Day 1 and prior to discharge on Day 8 or at early termination A 12-lead ECG will be conducted on the first day of screening and immediately prior to admission Four hours after receiving the first dose of study medication on Days 1-7 a 12-lead ECG will also be conducted A 12-lead ECG will be done prior to discharge on Day 8 or at early termination If in the opinion of the investigator clinically significant changes are noted on the ECG these measurements should be performed more frequently Additionally the next scheduled dose of study medication may be withheld at the discretion of the investigator or the subject may be discontinued from the study Subjects will be awakened and weighed each morning prior to breakfast Vital signs systolic and diastolic blood pressure heart rate respiration rate and body temperature are to be measured 3 hours after each dose of study medication at 0800 1300 and 1800 on Days 1-7 and prior to discharge on Day 8 For the orthostatic blood pressure readings subjects will remain sitting for 3 minutes prior to a blood pressure reading and then stand for 1 minute prior to a second blood pressure reading Clinical lab tests will be done during Screening on Day 7 or early termination and as needed at the physicians discretion The urine sample collected on the first day of Screening will be divided into two aliquots One sample will go to the local lab for confirmatory drug testing The other sample will be used for immediate dip-stick analysis of pregnancy for the female patients only A second dip-stick pregnancy test will be done during Baseline prior to randomization Adverse events and concomitant medication use will be assessed every day during the study Days 1-8
Subjects who demonstrate symptoms of withdrawal will be treated with a standard of care using the concomitant medications listed in Section 1311 At subjects request and at any time subject can be discontinued from the study without prejudice and will be medically stabilized subject will then be referred at subjects expense for further treatment
Analysis The primary outcome measures and each of the secondary outcome measures will be analyzed using appropriate statistical methods for the intent-to-treat the evaluable and for the completer groups The Intent-to-Treat ITT group is defined as the subjects who are randomized to treatment The evaluable group is defined as subjects in the ITT group who receive at least one dose of study medication and complete the post-medication SOWS on Day 1 The completer group will consist of all patients in the ITT group who meet the following criteria receive at least one dose of study drug on Day 5 and complete the SOWS-Gossop assessment on Day 5
It is hypothesized that lofexidine treatment compared to placebo will be associated with a significant reduction in opiate withdrawal symptoms All statistical tests will be two-sided at 5 Type-I error rate Confidence intervals will be two-sided with a 95 confidence coefficient
Summaries of the characteristics of the subject population in both treatment groups at baseline will be prepared for the modified intent-to-treat group and the completer group A summary will be prepared to show dropoutsretention over time in each group and for subpopulations All adverse events will be reported quarterly indicating the counts of unique adverse events by body system and preferred term MedDRA coded as experienced by study subjects in both the groups Laboratory data physical examinations and vital signs will be reported in tabular form
Secondary Objectives Secondary objectives include determining Lofexidines 1 Efficacy in the reduction in withdrawal symptoms in subjects undergoing opioid detoxification assessed by longitudinal changes in SOWS-Gossop OOWS-Handelsman VAS-E and MGCI subject and rater 2Efficacy in the reduction in the need of any concomitant medication to alleviate opiate withdrawal symptoms 3 Efficacy in increasing the number of completers during the treatment phase and 4 Safety in the study population
Study Design This is a randomized multi-center double blind placebo-controlled parallel-group study There are 3 major phases of the study During Phase I Screening screening assessments will be performed during Phase II Days 1-5 subjects will be admitted to an inpatient unit and randomized to receive either lofexidine 08 mg QID or placebo QID after the baseline assessments are performed prior to randomization on Day 1 and during Phase III Days 6-8 all subjects will receive placebo QID on Days 6-7 and then be discharged on Day 8 following the post-treatment assessments An adaptive randomization procedure will be used to randomly allocate subjects in one of the two treatment groups - lofexidine or placebo
Study Population 264 subjects with Diagnostic and Statistical Manual for Mental Disorders Fourth Edition DSM-IV criteria for current dependence on any opioid with a half-life similar to heroin or morphine determined by structured clinical interview SCID will be randomized in one of the treatment groups 132 subjects per group Subjects at least 18 years-of-age with positive urine toxicology screen for opiates and negative for methadone LAMLAAM or buprenorphine during screening with the ability to understand and provide written informed consent that meet all the inclusion criteria and do not meet any of the exclusion criteria may be randomized into the study
Treatments On Day 1 subjects are randomized to either lofexidine or placebo and receive lofexidine 08 mg 4 x 02 mg lofexidine tablets QID or placebo 4 matching placebo tablets QID Lofexidine or placebo will be administered orally within 15 minutes before or after 0800 1300 1800 and 2300 hours on Days 1-5 On Days 6 and 7 all subjects will receive placebo using the same dosing schedule as above
Efficacy Assessments The primary efficacy outcome measures will be the Short Opiate Withdrawal Scale SOWS-Gossop scores range 0-30 on Day 3 of the treatment phase defined as Days 1-5 and the number of days representing the duration of stay in the treatment program after randomization SOWS-Gossop will be administered once during Baseline on Day 1 prior to randomization and after 35 hours after the first dose on Days 1 - 7 Secondary outcome measures evaluating the treatment effects on opioid withdrawal symptoms include the proportion of subjects requiring any concomitant medication to alleviate opiate withdrawal symptoms and the proportion of subjects who are completers In addition the composite longitudinal scores of the SOWS-Gossop Objective Opiate Withdrawal Scale OOWS-Handelsman Modified Global Clinical Impression Scale Subject and Rater and Visual Analog Scale - Efficacy VAS-E will also be used to assess the treatment efficacy to reduce the withdrawal symptoms OOWS-Handelsman MGCI Subject and Rater and VAS-E will be administered once during Baseline on Day 1 prior to randomization and 35 hours after the first dose on Days 1-7
Safety Assessments After signing the informed consent and completing the consent quiz the subject will complete Screening assessments to determine eligibility for study enrollment A complete physical examination will be performed on the first day of screening A repeat physical exam will be performed at 3-4 hours after randomization on Day 1 and prior to discharge on Day 8 or at early termination A 12-lead ECG will be conducted on the first day of screening and immediately prior to admission Four hours after receiving the first dose of study medication on Days 1-7 a 12-lead ECG will also be conducted A 12-lead ECG will be done prior to discharge on Day 8 or at early termination If in the opinion of the investigator clinically significant changes are noted on the ECG these measurements should be performed more frequently Additionally the next scheduled dose of study medication may be withheld at the discretion of the investigator or the subject may be discontinued from the study Subjects will be awakened and weighed each morning prior to breakfast Vital signs systolic and diastolic blood pressure heart rate respiration rate and body temperature are to be measured 3 hours after each dose of study medication at 0800 1300 and 1800 on Days 1-7 and prior to discharge on Day 8 For the orthostatic blood pressure readings subjects will remain sitting for 3 minutes prior to a blood pressure reading and then stand for 1 minute prior to a second blood pressure reading Clinical lab tests will be done during Screening on Day 7 or early termination and as needed at the physicians discretion The urine sample collected on the first day of Screening will be divided into two aliquots One sample will go to the local lab for confirmatory drug testing The other sample will be used for immediate dip-stick analysis of pregnancy for the female patients only A second dip-stick pregnancy test will be done during Baseline prior to randomization Adverse events and concomitant medication use will be assessed every day during the study Days 1-8
Subjects who demonstrate symptoms of withdrawal will be treated with a standard of care using the concomitant medications listed in Section 1311 At subjects request and at any time subject can be discontinued from the study without prejudice and will be medically stabilized subject will then be referred at subjects expense for further treatment
Analysis The primary outcome measures and each of the secondary outcome measures will be analyzed using appropriate statistical methods for the intent-to-treat the evaluable and for the completer groups The Intent-to-Treat ITT group is defined as the subjects who are randomized to treatment The evaluable group is defined as subjects in the ITT group who receive at least one dose of study medication and complete the post-medication SOWS on Day 1 The completer group will consist of all patients in the ITT group who meet the following criteria receive at least one dose of study drug on Day 5 and complete the SOWS-Gossop assessment on Day 5
It is hypothesized that lofexidine treatment compared to placebo will be associated with a significant reduction in opiate withdrawal symptoms All statistical tests will be two-sided at 5 Type-I error rate Confidence intervals will be two-sided with a 95 confidence coefficient
Summaries of the characteristics of the subject population in both treatment groups at baseline will be prepared for the modified intent-to-treat group and the completer group A summary will be prepared to show dropoutsretention over time in each group and for subpopulations All adverse events will be reported quarterly indicating the counts of unique adverse events by body system and preferred term MedDRA coded as experienced by study subjects in both the groups Laboratory data physical examinations and vital signs will be reported in tabular form
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| USWM-001 | None | None | None |