Rheumatoid ArthritisPhase 1NCT02456844
Study to Investigate the Effect of BMS-986142 on the Pharmacokinetics (PK) of Methotrexate and Probe Substrate Cocktail in Healthy Patients
A Phase 1 study testing Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 and Methotrexate, Leucovorin and BMS-986142 in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb.
Trial summary
To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 and Methotrexate, Leucovorin and BMS-986142
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- May 2015to Jul 2015
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Groups 1 and 2:
- Written informed consent from all subjects.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- Non-smokers.
- Normal renal function at screening as evidenced by an estimated glomerular filtration rate (GFR) of > 90 mL/min/1.73 m2 .
- Subject reenrollment.
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- Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of BMS-986142.
- Male subjects must be willing to refrain from sperm donation during the entire study plus 5 half-lives of BMS-986142.
- Group 1 only:
- Healthy male and female (not of childbearing potential) subjects as determined by medical history, and clinical assessments.
- Women must have documented proof that they are not of childbearing potential and must not be breast feeding.
- Group 2 only:
- 1. Healthy male subjects as determined by medical history, and clinical assessments.
Who cannot join
- Administration of live vaccine including polio vaccine during the course of the study, 12 weeks prior to the first dose of study drug, or 30 days after the last dose of study drug.
- Active tuberculosis (TB) requiring treatment within the previous 3 years.
- History of herpes zoster.
- Subjects who have experienced recent infection, upper respiratory infection,.
About this study
Official title: Effects of BMS-986142 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates Montelukast (CYP2C8), Flurbiprofen (CYP2C9), Midazolam (CYP3A4), Digoxin (P-gp), and Pravastatin (OATP1B1) in Healthy Subjects
To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142, Methotrexate, Leucovorin and BMS-986142
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142Drug
- Montelukast 10-mg tablet: On Days 1 and 8,Single oral dose
- Flurbiprofen 50-mg tablet: On Days 1 and 8,Single oral dose
- Midazolam syrup 2.5 mL × 2 mg/mL (5 mg): On Days 1 and 8,Single oral dose
- Digoxin (Lanoxin®) 0.25 mg tablet: On Days 1 and 8,Single oral dose
- Pravastatin 40-mg tablet: On Days 1 and 8,Single oral dose
- BMS-986142: On Days 6 through 12.
Methotrexate, Leucovorin and BMS-986142Drug
- Methotrexate (MTX) single oral dose of 3 × 2.5-mg tablet (Days 1 and 8)
- Leucovorin single oral dose of 15-mg tablet (Days 2 and 9; 24 hours after MTX administration)
- BMS-986142 on Days 6 through 10.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 Receives: Drug: Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 |
| Group 2 | Experimental | Methotrexate,Leucovorin and BMS-986142 Receives: Drug: Methotrexate, Leucovorin and BMS-986142 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax)
Measured: Days 1 through 10
Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)
Measured: Days 1 through 10
Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)
Measured: Days 1 through 10
Secondary outcomes (7)
Time of maximum observed plasma concentration (Tmax)
Measured: Days 1 through 10
Terminal plasma half-life (T-half)
Measured: Days 1 through 10
Apparent total body clearance (parents only), CLT/F
Measured: Days 1 through 10
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight
Measured: Days 1 through 10
Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight
Measured: Days 1 through 10
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight
Measured: Days 1 through 10
Trough observed plasma concentration (For BMS-986142 only)
Measured: Days 1 through 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas L Hunt, MD PhD, Principal investigator, PPD Development, LP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456844
- Sponsor's protocol ID
- IM006-003
- Status last verified
- Jan 2016
- First submitted
- 27 May 2015
- Last updated
- 1 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of BMS-986142 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates Montelukast (CYP2C8), Flurbiprofen (CYP2C9), Midazolam (CYP3A4), Digoxin (P-gp), and Pravastatin (OATP1B1) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02456844
- Acronym / sponsor ID
- IM006-003
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 29 May 2015 (estimated)
- 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.
To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 |
| Group 2 | Experimental | Drug: Methotrexate, Leucovorin and BMS-986142Methotrexate,Leucovorin and BMS-986142 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Written informed consent from all subjects.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- Non-smokers.
- Normal renal function at screening as evidenced by an estimated glomerular filtration rate (GFR) of > 90 mL/min/1.73 m2 .
- Subject reenrollment.
Key exclusion criteria (4 listed)
- Administration of live vaccine including polio vaccine during the course of the study, 12 weeks prior to the first dose of study drug, or 30 days after the last dose of study drug.
- Active tuberculosis (TB) requiring treatment within the previous 3 years.
- History of herpes zoster.
- Subjects who have experienced recent infection, upper respiratory infection,.
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 |
|---|---|---|
| Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-9861421. Montelukast 10-mg tablet: On Days 1 and 8,Single oral dose 2. Flurbiprofen 50-mg tablet: On Days 1 and 8,Single oral dose 3. Midazolam syrup 2.5 mL × 2 mg/mL (5 mg): On Days 1 and 8,Single oral dose 4. Digoxin (Lanoxin®) 0.25 mg tablet: On Days 1 and 8,Single oral dose 5. Pravastatin 40-mg tablet: On Days 1 and 8,Single oral dose 6. BMS-986142: On Days 6 through 12. | Drug | Group 1 |
| Methotrexate, Leucovorin and BMS-9861421. Methotrexate (MTX) single oral dose of 3 × 2.5-mg tablet (Days 1 and 8) 2. Leucovorin single oral dose of 15-mg tablet (Days 2 and 9; 24 hours after MTX administration) 3. BMS-986142 on Days 6 through 10. | Drug | Group 2 |
Primary outcome
Maximum observed plasma concentration (Cmax)
Time frame: Days 1 through 10
Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)
Time frame: Days 1 through 10
Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)
Time frame: Days 1 through 10
7 secondary outcomes
Time of maximum observed plasma concentration (Tmax)
Time frame: Days 1 through 10
Terminal plasma half-life (T-half)
Time frame: Days 1 through 10
Apparent total body clearance (parents only), CLT/F
Time frame: Days 1 through 10
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight
Time frame: Days 1 through 10
Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight
Time frame: Days 1 through 10
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight
Time frame: Days 1 through 10
Trough observed plasma concentration (For BMS-986142 only)
Time frame: Days 1 through 10
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 1 Feb 2016.
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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.
Thomas L Hunt, MD PhD principal investigator
PPD Development, LP
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 and Methotrexate, Leucovorin and BMS-986142 in people with Rheumatoid Arthritis, run by Bristol-Myers Squibb.
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 13 inclusion and 4 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 1 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
Maximum observed plasma concentration (Cmax) (time frame: Days 1 through 10). The study lists 3 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 1 Feb 2016.