The Study is to Evaluate the Effect of Multiple Doses PF-06751979 on the Pharmacokinetics of Midazolam in Healthy Adults

Study Overview
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Brief Summary
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This is a drug interaction study to evaluate the PF-06751979 at steady state on the pharmacokinetics of oral midazolam single doses in fixed sequences including single dose midazolam alone in period 1 followed by multiple doses of 100 mg PF-06751979 once a day for 11 days with single dose midazolam co-administered on Day 10 in period 2

Official Title
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A Phase 1, Open-label, Fixed-sequence Design Study To Assess The Effect Of Multiple Dose Administration Of Pf-06751979 On The Single Dose Pharmacokinetics Of Oral Midazolam In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: midazolam
* Drug: PF-06751979


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female subjects of nonchildbearing potential and male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12-lead electrocardiogram (ECG), or clinical laboratory tests. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, (including alcoholic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and hereditary liver diseases), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Any condition possibly affecting drug absorption (eg, gastrectomy). Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product (whichever is longer). Subjects who have previously received PF-06751979. Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. As an exception, acetaminophen/paracetamol may be used at doses of <=1 g/day. Limited use of nonprescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor. Herbal supplements and hormone replacement therapy must have been discontinued at least 28 days prior to the first dose of investigational product. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing. History of hypersensitivity to midazolam or any other benzodiazapine. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral midazolam alone<br>single dose of oral midazolam administered alone in period 1 | Drug: midazolam<br>* a single oral dose of 2 mg midazolam<br>|
| Experimental: oral midazolam administered with multiple doses of PF-06751979<br>single dose of midazolam on day 10 with multiple doses of PF-06751979 once a day on Days 1-11 in period 2 | Drug: midazolam<br>* a single oral dose of 2 mg midazolam<br>Drug: PF-06751979<br>* multiple oral doses of PF-06751979 100 mg a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| midazolam Area Under the Curve from time 0 to last quantifiable concentration (AUClast) in Period 1 | the plasma midazolam AUC from 0 to tlast (time of last quantifiable concentration) when a single oral midazolam dose given alone | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hrs post-dose | 
| midazolam Cmax on Day 1 in Period 1 | the midazolam Cmax when single oral midazolam dose given alone | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hrs post-dose | 
| midazolam Area Under the Curve from time 0 to infinite (AUCinf) in Period 1 | the plasma midazolam AUC from 0 to infinity when a single oral midazolam dose given alone | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hrs post-dose | 
| midazolam AUClast in Period 2 | the plasma midazolam AUC from 0 to tlast (time of the last quantifiable concentration) when a single oral midazolam given in presence of steady state PF-06751979 | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 hrs post-dose | 
| midazolam Cmax in Period 2 | the midazolam Cmax when a single oral midazolam given in presence of steady state PF-06751979 | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 hrs post-dose | 
| midazolam AUCinf in Period 2 | the plasma midazolam AUC from 0 to infinity when a single oral midazolam given in presence of steady state PF-06751979 | 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 hrs post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug interaction, PF-06751979, oral midazolam