Trial Outcomes & Findings for A Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects (NCT NCT03493698)
NCT ID: NCT03493698
Last Updated: 2020-10-08
Results Overview
Comparison of Cmax for midazolam between Treatments A and D.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
17 participants
Primary outcome timeframe
Day 1 Treatment A and Day 19 Treatment D, respectively
Results posted on
2020-10-08
Participant Flow
Each subject was expected to complete treatment groups A, B, C and D; sequentially.
Participant milestones
| Measure |
Sequential Single, Multi-day & Combo Midazolam and Inarigivir
A: All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
D: All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
|
|---|---|
|
Treatment Period A
STARTED
|
17
|
|
Treatment Period A
COMPLETED
|
17
|
|
Treatment Period A
NOT COMPLETED
|
0
|
|
Treatment Period B
STARTED
|
17
|
|
Treatment Period B
COMPLETED
|
17
|
|
Treatment Period B
NOT COMPLETED
|
0
|
|
Treatment Period C
STARTED
|
17
|
|
Treatment Period C
COMPLETED
|
15
|
|
Treatment Period C
NOT COMPLETED
|
2
|
|
Treatment Period D
STARTED
|
15
|
|
Treatment Period D
COMPLETED
|
15
|
|
Treatment Period D
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Sequential Single, Multi-day & Combo Midazolam and Inarigivir
A: All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
D: All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
|
|---|---|
|
Treatment Period C
Adverse Event
|
1
|
|
Treatment Period C
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects
Baseline characteristics by cohort
| Measure |
Sequential Single, Multi-day & Combo Midazolam and Inarigivir
n=17 Participants
A: All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
D: All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
|
|---|---|
|
Age, Continuous
|
30 years
STANDARD_DEVIATION 9 • n=39 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Region of Enrollment
Netherlands
|
17 Participants
n=39 Participants
|
|
BMI
|
25.5 kg/m^2
STANDARD_DEVIATION 3.1 • n=39 Participants
|
PRIMARY outcome
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectivelyPopulation: All subjects who received at least one dose of midazolam and had sufficient concentration-time data to reliably estimate PK parameters
Comparison of Cmax for midazolam between Treatments A and D.
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 Participants
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)
|
12.4 ng/mL
Interval 6.19 to 21.4
|
—
|
13.0 ng/mL
Interval 7.54 to 21.0
|
—
|
PRIMARY outcome
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectivelyPopulation: This outcome measure was prespecified for treatment groups A and D only.
Comparison of AUC0-t for midazolam between Treatments A and D.
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 Participants
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)
|
29.9 h.ng/ml
Interval 16.2 to 57.7
|
—
|
28.7 h.ng/ml
Interval 15.6 to 44.6
|
—
|
PRIMARY outcome
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectivelyPopulation: This outcome measure was prespecified for treatment groups A and D only.
Comparison of AUC0-inf for midazolam between Treatments A and D.
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 Participants
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )
|
31.5 h.ng/ml
Interval 16.7 to 61.6
|
—
|
30.5 h.ng/ml
Interval 16.6 to 49.4
|
—
|
SECONDARY outcome
Timeframe: Day -1 to Day 20 and Follow-up (5-9 days post-treatment)Population: All participants analyzed
Safety and tolerability were measured via clinical laboratory evaluations, vital signs, 12-lead ECG, or physical examination
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
n=15 Participants
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 Participants
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 Participants
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 3 and Day 6 to 19Population: All subjects in treatment arms B and D who received inarigivir and had sufficient concentration-time data to reliably estimate PK parameters
A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D)
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
n=15 Participants
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
Day 3 AUC0-t (h.ng/mL)
|
0.914 h.ng/ml
Interval 0.129 to 3.23
|
—
|
—
|
—
|
|
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
Day 3AUC0-inf (h.ng/mL)
|
1.19 h.ng/ml
Interval 0.609 to 2.44
|
—
|
—
|
—
|
|
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
Day 19 AUC0-t (h.ng/mL)
|
—
|
0.951 h.ng/ml
Interval 0.238 to 2.26
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 3 and Day 6 to 19Population: All subjects in treatment arms B and D who received inarigivir and had sufficient concentration-time data to reliably estimate PK parameters
A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D)
Outcome measures
| Measure |
Treatment A: Midazolam
n=17 Participants
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B and C: Inarigivir
n=15 Participants
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax)
|
0.886 ng/mL
Interval 0.182 to 2.77
|
0.991 ng/mL
Interval 0.221 to 4.07
|
—
|
—
|
Adverse Events
Treatment A: Midazolam
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment B: Inarigivir
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment C: Inarigivir
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Treatment D: Inarigivir With Midazolam
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: Midazolam
n=17 participants at risk
All subjects will receive a single oral dose of 2 mg Midazolam on Day 1
Midazolam: Midazolam
|
Treatment B: Inarigivir
n=17 participants at risk
B: All subjects will receive a single oral dose of 400 mg Inarigivir on Day 3
Inarigivir: Inarigivir
|
Treatment C: Inarigivir
n=17 participants at risk；n=15 participants at risk
C: All subjects receive oral dose of 400 mg Inarigivir once daily from Day 6 to Day 18
Inarigivir: Inarigivir
|
Treatment D: Inarigivir With Midazolam
n=15 participants at risk
All subjects will receive a single oral dose of 400 mg Inarigivir coadministered with a single oral dose of 2 mg Midazolam on Day 19
Midazolam: Midazolam
Inarigivir: Inarigivir
|
|---|---|---|---|---|
|
General disorders
Fatigue
|
5.9%
1/17 • 20 days
|
11.8%
2/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
General disorders
Influenza Like Illness
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
General disorders
Sensation of Foreign Body
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Gastrointestinal disorders
Aphthous Ulcer
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Gastrointestinal disorders
Diarrhea
|
5.9%
1/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Gastrointestinal disorders
Dry Mouth
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.9%
1/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
6.7%
1/15 • 20 days
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal Discomfort
|
5.9%
1/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Nervous system disorders
Headache
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
5.9%
1/17 • Number of events 2 • 20 days
|
0.00%
0/15 • 20 days
|
|
Eye disorders
Dry eye
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Psychiatric disorders
Affect Lability
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
6.7%
1/15 • 20 days
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Skin and subcutaneous tissue disorders
Skin Fissures
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
5.9%
1/17 • 20 days
|
0.00%
0/15 • 20 days
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/17 • 20 days
|
0.00%
0/17 • 20 days
|
11.8%
2/17 • 20 days
|
0.00%
0/15 • 20 days
|
Additional Information
Don Mitchell, Vice President, Operations & Corporate Development
Spring Bank Pharmaceuticals, Inc.
Phone: (508) 689-9737
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place