Trial Outcomes & Findings for Evaluation of Effect of Vonoprazan on Midazolam Pharmacokinetics in Healthy Participants (NCT NCT04545944)

NCT ID: NCT04545944

Last Updated: 2023-03-17

Results Overview

AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

Results posted on

2023-03-17

Participant Flow

20 participants were enrolled at a single study center in the United States.

32 participants were screened, 12 of which were screen failures. The remaining 20 were enrolled and received study treatment.

Participant milestones

Participant milestones
Measure	All Participants All participants were administered single oral doses of 2 milligrams (mg) of midazolam syrup on Day 1 and Day 9 and twice per day (BID) oral doses of 20 mg vonoprazan tablets on Days 2 through 10.
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Effect of Vonoprazan on Midazolam Pharmacokinetics in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=20 Participants All participants were administered single oral doses of 2 mg of midazolam syrup on Day 1 and Day 9 and BID oral doses of 20 mg vonoprazan tablets on Days 2 through 10.
Age, Continuous	32.3 years STANDARD_DEVIATION 7.17 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

Population: The pharmacokinetics (PK) population included participants who received at least one dose of study drug and had sufficient concentration data to support accurate estimation of at least one PK parameter. Participants who experienced vomiting within two times the median time to maximum observed plasma concentration (Tmax) after midazolam dosing were excluded from the PK analysis.

AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.

Outcome measures

Outcome measures
Measure	Midazolam Alone n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 1.	Midazolam With Vonoprazan n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 9 and BID oral doses of 20 mg vonoprazan tablets on Day 2 to Day 10.
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam	24.2 Nanogram Hours per Milliliter (ng•h/mL) Standard Deviation 8.76	50.7 Nanogram Hours per Milliliter (ng•h/mL) Standard Deviation 39.8

PRIMARY outcome

Population: The PK population included participants who received at least one dose of study drug and had sufficient concentration data to support accurate estimation of at least one PK parameter. Participants who experienced vomiting within two times the median time to maximum observed plasma concentration (Tmax) after midazolam dosing were excluded from the PK analysis.

AUC0-inf was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.

Outcome measures

Outcome measures
Measure	Midazolam Alone n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 1.	Midazolam With Vonoprazan n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 9 and BID oral doses of 20 mg vonoprazan tablets on Day 2 to Day 10.
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam	25.5 Nanogram Hours per Milliliter (ng•h/mL) Standard Deviation 9.00	52.3 Nanogram Hours per Milliliter (ng•h/mL) Standard Deviation 39.8

PRIMARY outcome

Cmax was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9.

Outcome measures

Outcome measures
Measure	Midazolam Alone n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 1.	Midazolam With Vonoprazan n=20 Participants Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 9 and BID oral doses of 20 mg vonoprazan tablets on Day 2 to Day 10.
Maximum Observed Plasma Concentration (Cmax) of Midazolam	10.3 Nanograms per Milliliter (ng/mL) Standard Deviation 3.61	20.3 Nanograms per Milliliter (ng/mL) Standard Deviation 9.55

Adverse Events

Midazolam Alone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Vonoprazan Alone

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Midazolam With Vonoprazan

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Midazolam Alone n=20 participants at risk Participants were administered a single oral dose of 2 mg of midazolam syrup on Day 1.	Vonoprazan Alone n=20 participants at risk Participants were administered BID oral doses of 20 mg vonoprazan tablets alone on Day 2 through Day 8.	Midazolam With Vonoprazan n=20 participants at risk Participants were administered single oral doses of 2 mg of midazolam syrup on Day 9 and BID oral doses of 20 mg vonoprazan tablets on Days 9 and 10.
Nervous system disorders Dizziness	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Nervous system disorders Headache	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Nervous system disorders Somnolence	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Gastrointestinal disorders Nausea	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	10.0% 2/20 • Number of events 2 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
General disorders Feeling drunk	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	5.0% 1/20 • Number of events 1 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.	0.00% 0/20 • Day 1 to Day 25 The safety population included all participants who received at least one dose of study drug. Treatment-emergent adverse events were summarized by treatment (midazolam alone, vonoprazan alone and midazolam with vonoprazan) and an event was assigned to the last treatment the participant received when the event occurred.

Additional Information

Phathom Medical Information

Phathom Pharmaceuticals, Inc.

Phone: 1-888-775-PHAT (7428)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PPD cannot publish data from a Phathom trial (or assist a third party with a publication) that includes any vonoprazan data without consent.
Publication restrictions are in place

Restriction type: OTHER