A Drug Drug Interaction Study Between PF-06826647 And Oral Contraceptive Steroids In Healthy Female Participants

A PHASE 1, RANDOMIZED, OPEN LABEL, FIXED SEQUENCE STUDY TO ESTIMATE THE EFFECT OF PF-06826647 ON THE PHARMACOKINETICS OF ORAL CONTRACEPTIVE STEROIDS AND TO ESTIMATE THE EFFECT OF ORAL CONTRACEPTIVE STEROIDS ON PHARMACOKINETICS OF PF-06826647 IN HEALTHY FEMALE PARTICIPANTS

This is a Phase 1, fixed sequence, multiple dose, open label study of the effect of PF-06826647 on oral contraceptive (OC) pharmacokinetics (PK) and vice versa in healthy female participants. A total of approximately 15 healthy female participants will be enrolled and dosed to achieve at least 12 participants completing the study.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06826647; Drug: Oral Contraceptive (OC)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Quotient Sciences Screening Office
    • Miami, Florida, United States, 33126
      • Quotient Sciences-Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 1. Healthy female participants of non-childbearing potential must be 18 to 60 years of age, inclusive
• 2. Female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, including blood pressure (BP) and pulse rate measurement, laboratory tests, and 12 lead ECG
• 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
• 4. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)

Exclusion Criteria:

• 1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• 2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• 3. History of venous and arterial thrombosis (ie, deep venous thrombosis, pulmonary embolism) or hereditary clotting disorders (in first degree immediate relatives).
• 4. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
• 5. Any current evidence of untreated active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB).
• 6. Participants who use tobacco or nicotine containing products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PF-06826647 alone then OC alone then OC+PF-06826647; In Period 1 (Period 1 is 2 days), participants will receive a single dose of PF-06826647 600 mg on Day 1. Period 2 (Period 2 is 14 days) will immediately follow Period 1 without any washout. In Period 2, the participants will receive OC in the form of 1 PORTIA (30 µg EE and 150 µg LN) or equivalent tablet, orally starting from Period 2 Day 1 until Period 3-Day 16 (Period 3 is 17 Days). Period 3 will immediately follow Period 2 with no washout. In Period 3 on Day 1, the participants will receive a single dose of PF-06826647 600 mg. On Day 2 in Period 3, PF-06826647 will not be dosed. From Day 3, the participants will receive PF-06826647 600 mg QD for 14 days followed by OC in the form of 1 PORTIA (EE and LN) or equivalent tablet.

Drug: PF-06826647; 100 mg tablet; Drug: Oral Contraceptive (OC); OC in the form of 1 PORTIA (30 µg EE and 150 µg LN) or equivalent tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUGtau) of Ethinyl Estradiol (EE)	Area under the plasma concentration time profile from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.	Day 14 in Period 2 (Period 2 is 14 days) and Day 16 in Period 3 (Period 3 is 17 days)
Area Under the Plasma Concentration-Time Profile From Time Zero To End of Dosing Interval (AUGtau) of Levonorgestrel (LN)	Area under the plasma concentration time profile from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.	Day 14 in Period 2 (Period 2 is 14 days) and Day 16 in Period 3 (Period 3 is 17 days)
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06826647	AUCinf is calculated by AUClast + (Clast*/kel), where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Day 1 in Period 1 (Period 1 is 2 days) and Period 3 (Period 3 is 17 days)
Maximum Plasma Concentration (Cmax) of PF-06826647	Cmax will be observed directly from data.	Day 1 in Period 1 (Period 1 is 2 days) and Period 3 (Period 3 is 17 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment.	Baseline in Period 1 (Period 1 is 2 days) to Day 17 in Period 3 (Period 3 is 17 days)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), and pulse rate.	Baseline in Period 1 (Period 1 is 2 days) to Day 17 in Period 3 (Period 3 is 17 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology	Hematology evaluation includes: hemoglobin, hematocrit, red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets, white blood cell count (WBC), neutrophils, eosinophils, monocytes, basophils, lymphocytes and reticulocytes.	Baseline in Period 1 (Period 1 is 2 days) to Day 17 in Period 3 (Period 3 is 17 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry	Clinical chemistry evaluation includes: blood urea nitrogen, creatinine, fasting glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, urate, albumin, protein, creatinine kinase	Baseline in Period 1 (Period 1 is 2 days) to Day 17 in Period 3 (Period 3 is 17 days)
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis	Urinalysis evaluation includes: qual urine glucose, qual protein, qual blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, urine leukocytes.	Baseline in Period 1 (Period 1 is 2 days) to Day 17 in Period 3 (Period 3 is 17 days)
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings	Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG	Baseline (Period 1 Day 1), Day 1 (Period 1 and Period 2) up to Day 17 (Period 3)

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): October 23, 2019
• Primary Completion (Actual): January 9, 2020
• Study Completion (Actual): January 9, 2020

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Oral contraceptive; Drug-Drug Interaction (DDI); PF-06826647
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral
• Other Study ID Numbers: C2501005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/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