HealthyPhase 1NCT03637049
Effect of PBI-4050 on the Pharmacokinetics of Midazolam in Heathy Adult Subjects
A Phase 1 study testing PBI-4050 and midazolam in people with Healthy, run by Liminal BioSciences Ltd. at 1 site in United States.
Trial summary
This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of PBI-4050 combined with midazolam in healthy adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- PBI-4050 and midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2018to 22 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males or females (WONCBP only).
- Age 18-65 years.
- Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing.
- Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
- Generally good health.
- Males willing to use appropriate contraception.
Who cannot join
- Significant medical history or physical findings.
- History or presence of drug allergy or hypersensitivity to treatment ingredients.
- Gastrointestinal surgery.
- Pregnant or lactating.
- Positive urine drug or alcohol screen.
- Abnormal heart rate or blood pressure.
Show all 12Show fewer
- Prescribed systemic or topical medication taken recently, or supplements/remedies interfering with study procedures or safety.
- Receiving drugs known as significant inducers of CYP2C9, CYP3A4, CYP2C8 and/or CYP1A2 enzymes and/or P-glycoprotein, including St. John's Wort, for 28 days prior to the first dosing and throughout the study.
- Has been on a diet incompatible with the on-study diet.
- Recent blood donation or significant blood loss.
- Recent blood received.
- Participation in another clinical study within 30 days prior to the first.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of PBI-4050 on the Pharmacokinetics of Midazolam, a Sensitive Cytochrome P450 3A Substrate, in Healthy Adult Subjects
This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of PBI-4050 combined with midazolam in healthy adult subjects.
Read the detailed description
This is a Phase 1, single-center, open-label, 2-period, fixed sequence study to investigate the effect of multiple doses of PBI-4050 on the PK of midazolam, a cytochrome P450 (CYP) 3A substrate, in healthy adult men and healthy women of non-childbearing potential (WONCBP), and to determine the safety and tolerability of PBI-4050, when co-administered with midazolam.
On Day 1 of Period 1, subjects will receive a single oral dose of midazolam followed by PK sampling of midazolam and its metabolite 1-hydroxymidazolam (1-OH-midazolam). In Period 2, subjects will receive multiple daily doses of PBI-4050 for 5 consecutive days (Day 1 to Day 5) with a single oral dose of midazolam co-administered on Day 5. PK sampling for midazolam and 1-OH-midazolam will be collected for 24 hours following dosing on Day 5. PK sampling for PBI-4050 and its major metabolite will be collected at pre-dose on Days 3, 4, and 5.
There will be a washout period of at least 2 days between midazolam dose in Period 1 and the first PBI-4050 dose in Period 2.
- Conditions
- Healthy
- Being tested
- PBI-4050 and midazolam
- Keywords
- PBI-4050, drug-drug interaction, CYP3A, midazolam, healthy subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBI-4050 and midazolamDrug
A single oral dose of midazolam (1 mL of 2mg/mL syrup) will be given to all subjects in Period 1 and on Day 5 of Period 2. 1200 mg of PBI-4050 (3 X 400 mg tablets) will be administered for 5 days (Day 1 to Day 5) of Period 2 and a single dose of midazolam (1 mL of 2mg/mL) on Day 5.
| Study group | Role | What they receive |
|---|---|---|
| PBI-4050 and midazolam | Experimental | Midazolam 2 mg solution once (Period 1), PBI-4050 1200 mg (3 x 400 mg tablets) once per day for 5 days and midazolam 2 mg solution once on last day (Period 2). Receives: Drug: PBI-4050 and midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in area under the concentration-time curve (AUC0-t) for midazolam and 1-OH-midazolam in presence of PBI-4050
AUC0-t (AUC from time 0 to last observed non-zero concentration) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Measured: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
Change in area under the concentration-time curve (AUC0-inf) for midazolam and 1-OH-midazolam in presence of PBI-4050
AUC0-inf (AUC from time 0 extrapolated to infinity) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Measured: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
Change in maximum plasma concentration (Cmax) for midazolam and 1-OH-midazolam in presence of PBI-4050
Cmax of midazolam and 1-OH-midazolam assessed on Day 1(Period 1) and Day 5 (Period 2)
Measured: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
Change in concentration observed at the end of the dosing interval (Ctrough) for plasma PBI-4050 and its major metabolite
Ctrough is the concentration observed at the end of the dosing interval in Period 2.
Measured: PK sampling for PBI-4050 and its metabolite done at pre-dose on Days 3, 4, and 5 of Peiod 2
Secondary outcomes (1)
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of subjects that experience Adverse Events (AEs).
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start17 Jul 2018
- Primary completion9 Aug 2018
- Study completion22 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Liminal BioSciences Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03637049
- Sponsor's protocol ID
- PBI-4050-CT-9-16
- Other IDs
- CA25590
- Status last verified
- Dec 2020
- First submitted
- 8 Aug 2018
- Last updated
- 8 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified individual participant data for all primary and secondary outcome measures may be made available upon request.
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of PBI-4050 on the Pharmacokinetics of Midazolam, a Sensitive Cytochrome P450 3A Substrate, in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03637049
- Acronym / sponsor ID
- PBI-4050-CT-9-16
- Conditions
- Healthy
- Keywords
- PBI-4050, drug-drug interaction, CYP3A, midazolam, healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Liminal BioSciences Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Celerion
- Study start
- 17 Jul 2018 (actual)
- Primary completion
- 9 Aug 2018 (actual)
- Study completion
- 22 Aug 2018 (actual)
- First posted
- 17 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the pharmacokinetics (PK) and safety of multiple doses of PBI-4050 combined with midazolam in healthy adult subjects.
Detailed description
This is a Phase 1, single-center, open-label, 2-period, fixed sequence study to investigate the effect of multiple doses of PBI-4050 on the PK of midazolam, a cytochrome P450 (CYP) 3A substrate, in healthy adult men and healthy women of non-childbearing potential (WONCBP), and to determine the safety and tolerability of PBI-4050, when co-administered with midazolam.
On Day 1 of Period 1, subjects will receive a single oral dose of midazolam followed by PK sampling of midazolam and its metabolite 1-hydroxymidazolam (1-OH-midazolam). In Period 2, subjects will receive multiple daily doses of PBI-4050 for 5 consecutive days (Day 1 to Day 5) with a single oral dose of midazolam co-administered on Day 5. PK sampling for midazolam and 1-OH-midazolam will be collected for 24 hours following dosing on Day 5. PK sampling for PBI-4050 and its major metabolite will be collected at pre-dose on Days 3, 4, and 5.
There will be a washout period of at least 2 days between midazolam dose in Period 1 and the first PBI-4050 dose in Period 2.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PBI-4050 and midazolam | Experimental | Drug: PBI-4050 and midazolamMidazolam 2 mg solution once (Period 1), PBI-4050 1200 mg (3 x 400 mg tablets) once per day for 5 days and midazolam 2 mg solution once on last day (Period 2). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Males or females (WONCBP only).
- Age 18-65 years.
- Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dosing.
- Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at screening.
- Generally good health.
Key exclusion criteria (12 listed)
- Significant medical history or physical findings.
- History or presence of drug allergy or hypersensitivity to treatment ingredients.
- Gastrointestinal surgery.
- Pregnant or lactating.
- Positive urine drug or alcohol screen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PBI-4050 and midazolamA single oral dose of midazolam (1 mL of 2mg/mL syrup) will be given to all subjects in Period 1 and on Day 5 of Period 2. 1200 mg of PBI-4050 (3 X 400 mg tablets) will be administered for 5 days (Day 1 to Day 5) of Period 2 and a single dose of midazolam (1 mL of 2mg/mL) on Day 5. | Drug | PBI-4050 and midazolam |
Primary outcome
Change in area under the concentration-time curve (AUC0-t) for midazolam and 1-OH-midazolam in presence of PBI-4050
Time frame: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
AUC0-t (AUC from time 0 to last observed non-zero concentration) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Change in area under the concentration-time curve (AUC0-inf) for midazolam and 1-OH-midazolam in presence of PBI-4050
Time frame: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
AUC0-inf (AUC from time 0 extrapolated to infinity) of midazolam and 1-OH-midazolam assessed on Day 1 (Period 1) and Day 5 (Period 2)
Change in maximum plasma concentration (Cmax) for midazolam and 1-OH-midazolam in presence of PBI-4050
Time frame: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2
Cmax of midazolam and 1-OH-midazolam assessed on Day 1(Period 1) and Day 5 (Period 2)
Change in concentration observed at the end of the dosing interval (Ctrough) for plasma PBI-4050 and its major metabolite
Time frame: PK sampling for PBI-4050 and its metabolite done at pre-dose on Days 3, 4, and 5 of Peiod 2
Ctrough is the concentration observed at the end of the dosing interval in Period 2.
1 secondary outcome
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Individual participant dataSharing planned: Undecided. De-identified individual participant data for all primary and secondary outcome measures may be made available upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBI-4050 and midazolam in people with Healthy, run by Liminal BioSciences Ltd. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in area under the concentration-time curve (AUC0-t) for midazolam and 1-OH-midazolam in presence of PBI-4050 (time frame: PK sampling at pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose on Day 1 in Period 1 and on Day 5 in Period 2). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2020.