Ignite Creation Date:
2025-12-25 @ 4:12 AM
Ignite Modification Date:
2025-12-26 @ 3:10 AM
Study NCT ID:
NCT04385420
Status:
COMPLETED
Last Update Posted:
2020-05-13
First Post:
2020-05-06
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Phase 1 Study of ATR-002
Sponsor:
Atriva Therapeutics GmbH
Organization:
Study Overview
Official Title:
Phase 1 Single Dose Escalation/Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, And Pharmacokinetics of Ascending Doses of a MEK Inhibitor (ATR-002) Given for 7 Days in Healthy Subjects
Status:
COMPLETED
Status Verified Date:
2020-05
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:
This was a combination of a single ascending dose (SAD) study to evaluate the safety, tolerability, and PK of 3 oral doses of a MEK inhibitor and a multiple ascending dose (MAD) study of 3 oral doses of a MEK inhibitor.
Subjects were to be enrolled in 3 different cohorts in the SAD and 3 different cohorts in the MAD and were to be randomly (blinded) allocated to active treatment or placebo (each cohort consisted of 8 subjects receiving active treatment and 2 subjects receiving placebo).
Subjects were to be enrolled in 3 different cohorts in the SAD and 3 different cohorts in the MAD and were to be randomly (blinded) allocated to active treatment or placebo (each cohort consisted of 8 subjects receiving active treatment and 2 subjects receiving placebo).
Detailed Description:
Each subject in the SAD cohorts was to receive a single dose of the MEK inhibitor ATR-002 (PD0184264), with a starting dose of 100 mg ATR-002 or placebo:
* Cohort 1: 100 mg ATR-002 or placebo;
* Cohort 2: 100 mg + X mg ATR-002 or placebo;
* Cohort 3: 100 mg + X mg + Y mg ATR-002 or placebo. An additional cohort (Cohort 4) of 10 subjects (4:1 active vs placebo) could have been recruited into the SAD Part, if appropriate.
Effectively, 4 cohorts were treated:
* Cohort 1: 100 mg ATR-002 or placebo;
* Cohort 2: 300 mg ATR-002 or placebo;
* Cohort 3: 600 mg ATR-002 or placebo;
* Cohort 4: 900 mg ATR-002 or placebo. Between each cohort, a blinded interim analysis of PK, safety and tolerability had to be performed. The available data was evaluated by the Investigator and sponsor in a Safety Review Committee (SRC) meeting.
Once a dose level was judged to be safe, the SRC determined the dose level for the next cohort considering a maximal increment of 400 mg compared to the previous cohort, and the next dose level could be administered to the next cohort.
The maximal dose level could not exceed 900 mg ATR-002. Each subject in the MAD cohorts was to receive once daily (QD) doses (fasted) of the MEK inhibitor ATR-002 for 7 days, starting with a dose of 100 mg ATR-002 or placebo QD.
* Cohort 5: 100 mg ATR-002 QD or placebo;
* Cohort 6: 100 mg + A mg ATR-002 QD or placebo;
* Cohort 7: 100 mg + A mg + B mg ATR-002 QD or placebo. An additional cohort (Cohort 8) of 10 subjects (4:1 active vs placebo) could be recruited into the MAD Part, if appropriate.
Effectively, 3 cohorts were treated:
* Cohort 5: 100 mg ATR-002 QD or placebo;
* Cohort 6: 300 mg ATR-002 QD or placebo;
* Cohort 7: 600 mg ATR-002 QD or placebo. Between each cohort, a blinded interim analysis of PK, safety and tolerability had to be performed. The available data was evaluated by the Investigator and sponsor in a SRC meeting. Once a dose level was judged to be safe, the SCR determined the dose level for the next cohort considering a maximal increment of 400 mg compared to the previous cohort, and the next dose level could be administered to the next cohort.
The maximal dose level could not exceed 900 mg ATR-002. During the study, no repeated daily dose could exceed the maximum single dose that has been shown to cause no safety concerns.
Subjects were resident on the ward from the day (late afternoon/evening) before dosing (Day -1) until completion of procedures at 96h following their final dose of study medication. They were to attend a follow up visit 28 days (± 2 days) following their final dose of study medication.
Subjects with AEs that were ongoing at the end of the study were followed up as appropriate until the AEs had resolved or stabilised, up to a maximum of 30 days after the last dose of study drug.
Pharmacokinetics were determined predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, postdose, and predose on Day 2-4 in the SAD Part, and predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, of Day 1 and Day 7, predose on Day 2-6 and 48h, 72h, and 96h post final dose of Day 7 in the MAD Part. The 72h and 96h samples in both SAD and MAD were only to be analysed if deemed informative based on the results of the 48h PK sample.
* Cohort 1: 100 mg ATR-002 or placebo;
* Cohort 2: 100 mg + X mg ATR-002 or placebo;
* Cohort 3: 100 mg + X mg + Y mg ATR-002 or placebo. An additional cohort (Cohort 4) of 10 subjects (4:1 active vs placebo) could have been recruited into the SAD Part, if appropriate.
Effectively, 4 cohorts were treated:
* Cohort 1: 100 mg ATR-002 or placebo;
* Cohort 2: 300 mg ATR-002 or placebo;
* Cohort 3: 600 mg ATR-002 or placebo;
* Cohort 4: 900 mg ATR-002 or placebo. Between each cohort, a blinded interim analysis of PK, safety and tolerability had to be performed. The available data was evaluated by the Investigator and sponsor in a Safety Review Committee (SRC) meeting.
Once a dose level was judged to be safe, the SRC determined the dose level for the next cohort considering a maximal increment of 400 mg compared to the previous cohort, and the next dose level could be administered to the next cohort.
The maximal dose level could not exceed 900 mg ATR-002. Each subject in the MAD cohorts was to receive once daily (QD) doses (fasted) of the MEK inhibitor ATR-002 for 7 days, starting with a dose of 100 mg ATR-002 or placebo QD.
* Cohort 5: 100 mg ATR-002 QD or placebo;
* Cohort 6: 100 mg + A mg ATR-002 QD or placebo;
* Cohort 7: 100 mg + A mg + B mg ATR-002 QD or placebo. An additional cohort (Cohort 8) of 10 subjects (4:1 active vs placebo) could be recruited into the MAD Part, if appropriate.
Effectively, 3 cohorts were treated:
* Cohort 5: 100 mg ATR-002 QD or placebo;
* Cohort 6: 300 mg ATR-002 QD or placebo;
* Cohort 7: 600 mg ATR-002 QD or placebo. Between each cohort, a blinded interim analysis of PK, safety and tolerability had to be performed. The available data was evaluated by the Investigator and sponsor in a SRC meeting. Once a dose level was judged to be safe, the SCR determined the dose level for the next cohort considering a maximal increment of 400 mg compared to the previous cohort, and the next dose level could be administered to the next cohort.
The maximal dose level could not exceed 900 mg ATR-002. During the study, no repeated daily dose could exceed the maximum single dose that has been shown to cause no safety concerns.
Subjects were resident on the ward from the day (late afternoon/evening) before dosing (Day -1) until completion of procedures at 96h following their final dose of study medication. They were to attend a follow up visit 28 days (± 2 days) following their final dose of study medication.
Subjects with AEs that were ongoing at the end of the study were followed up as appropriate until the AEs had resolved or stabilised, up to a maximum of 30 days after the last dose of study drug.
Pharmacokinetics were determined predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, postdose, and predose on Day 2-4 in the SAD Part, and predose 30 min, 1h, 2h, 4h, 8h, 12h, and 24h, of Day 1 and Day 7, predose on Day 2-6 and 48h, 72h, and 96h post final dose of Day 7 in the MAD Part. The 72h and 96h samples in both SAD and MAD were only to be analysed if deemed informative based on the results of the 48h PK sample.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: