Trial Outcomes & Findings for The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers (NCT NCT03831971)
NCT ID: NCT03831971
Last Updated: 2020-08-03
Results Overview
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
COMPLETED
PHASE1
26 participants
Day 1
2020-08-03
Participant Flow
26 subjects signed consent. 14 subjects not eligible. 12 subjects underwent study.
Participant milestones
| Measure |
ANS-6637 & Midazolam
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Influence of ANS-6637 on Midazolam Pharmacokinetics in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Time to Maximum Concentration of Midazolam Alone
|
0.58 hours
Geometric Coefficient of Variation 55.4
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam Alone
|
0.58 hours
Geometric Coefficient of Variation 55.4
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam Alone
|
14.28 ng/mL
Geometric Coefficient of Variation 46.5
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam Alone
|
9.04 ng/mL
Geometric Coefficient of Variation 65.3
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Plasma Exposure of Midazolam Alone
|
49.73 ng * h/mL
Geometric Coefficient of Variation 58.8
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
1-hydroxymidazolam plasma area under the concentration time curve (time 0-infinity). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam Alone
|
27.2 ng * h/mL
Geometric Coefficient of Variation 59.3
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Elimination of Midazolam Alone
|
4.68 hours
Geometric Coefficient of Variation 23.3
|
PRIMARY outcome
Timeframe: Day 1Population: Participants who received midazolam
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Elimination of 1-hydroxymidazolam Alone
|
5.29 hours
Geometric Coefficient of Variation 31.8
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Time to Maximum Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
|
0.69 hours
Geometric Coefficient of Variation 87.8
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Time to maximum plasma concentration (tmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Time to Maximum Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
|
0.69 hours
Geometric Coefficient of Variation 87.8
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Maximum Total Plasma Concentration of Midazolam: Midazolam Plus Steady State ANS-6637
|
17.47 ng/mL
Geometric Coefficient of Variation 37
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Maximum total plasma concentration (Cmax). The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Maximum Total Plasma Concentration of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
|
8.61 ng/mL
Geometric Coefficient of Variation 59.3
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Midazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Plasma Exposure of Midazolam: Midazolam Plus Steady State ANS-6637
|
62.63 ng * h/mL
Geometric Coefficient of Variation 46.7
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
1-hydroxymidazolam plasma area under the concentration time curve 0-infinity. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Plasma Exposure of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
|
29.28 ng * h/mL
Geometric Coefficient of Variation 53.3
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Elimination of Midazolam: Midazolam Plus Steady State ANS-6637
|
4.64 hours
Geometric Coefficient of Variation 20.1
|
PRIMARY outcome
Timeframe: Day 8Population: Participants who received midazolam and ANS-6637
Half-life. The summary PK results were informed by a continuous measurement at the following serial blood collection time points: 0 (pre-dose), then 0.5, 1, 2, 3, 4, 6, 8, 12, 22, and 24 hours postdose.
Outcome measures
| Measure |
ANS-6637 & Midazolam
n=12 Participants
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Pharmacokinetics - Elimination of 1-hydroxymidazolam: Midazolam Plus Steady State ANS-6637
|
5.76 hours
Geometric Coefficient of Variation 34.6
|
Adverse Events
ANS-6637 & Midazolam
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ANS-6637 & Midazolam
n=12 participants at risk
Subjects will receive (1) midazolam 5 mg po single dose on Day 1 followed by (2) Drug free period on Day 2 followed by (3) ANS-6637 600 mg po daily (Days 3-7) to reach steady state followed by (4) ANS-6637 600 mg po single dose + midazolam 5mg po single dose on Day 8
|
|---|---|
|
Cardiac disorders
Dizziness
|
8.3%
1/12 • 90 days
|
|
Cardiac disorders
Tachycardia
|
25.0%
3/12 • 90 days
|
|
General disorders
Fatigue
|
100.0%
12/12 • 90 days
|
|
General disorders
Pain
|
8.3%
1/12 • 90 days
|
|
Infections and infestations
Bacteriuria
|
25.0%
3/12 • 90 days
|
|
Investigations
Alanine aminotransferase increased
|
8.3%
1/12 • 90 days
|
|
Investigations
Amylase increased
|
25.0%
3/12 • 90 days
|
|
Investigations
Aspartate aminotransferase increased
|
8.3%
1/12 • 90 days
|
|
Investigations
Blood alkaline phosphatase increased
|
8.3%
1/12 • 90 days
|
|
Investigations
Blood bicarbonate abnormal
|
8.3%
1/12 • 90 days
|
|
Investigations
Blood cholesterol increased
|
33.3%
4/12 • 90 days
|
|
Investigations
Blood creatinine increased
|
8.3%
1/12 • 90 days
|
|
Investigations
Creatinine renal clearance decreased
|
41.7%
5/12 • 90 days
|
|
Investigations
Electrocardiogram PR prolongation
|
8.3%
1/12 • 90 days
|
|
Investigations
Urine analysis abnormal
|
8.3%
1/12 • 90 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • 90 days
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • 90 days
|
|
Nervous system disorders
Insomnia
|
8.3%
1/12 • 90 days
|
|
Psychiatric disorders
Depression
|
8.3%
1/12 • 90 days
|
|
Psychiatric disorders
Sleep disorder
|
8.3%
1/12 • 90 days
|
|
Renal and urinary disorders
Haematuria
|
8.3%
1/12 • 90 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.3%
1/12 • 90 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
1/12 • 90 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place