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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: midazolam; Drug: PF-06751979

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral midazolam alone; single dose of oral midazolam administered alone in period 1	Drug: midazolam; a single oral dose of 2 mg midazolam
Experimental: oral midazolam administered with multiple doses of PF-06751979; 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; a single oral dose of 2 mg midazolam; Drug: PF-06751979; multiple oral doses of PF-06751979 100 mg a day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Actual): July 11, 2017
• Study Completion (Actual): July 11, 2017

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 26, 2017
• Last Update Submitted That Met QC Criteria: July 24, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: drug interaction; oral midazolam; PF-06751979
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: B8271007; 2016-004238-50 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes