A Study To Estimate The Effect of PF-06650833 On The Pharmacokinetics (PK) of Oral Contraceptive (OC)

A PHASE 1, OPEN LABEL, FIXED SEQUENCE STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSE PF-06650833 ON THE PHARMACOKINETICS OF SINGLE DOSE ORAL CONTRACEPTIVE STEROIDS IN HEALTHY FEMALE PARTICIPANTS

This is a Phase 1, open label, fixed sequence study of the effect of multiple dose PF-06650833 on single dose OC PK in healthy female subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ethinyl estradiol (EE) and levonogestrel (LN); Drug: PF-06650833

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:

1. Healthy female subjects

2. Female subjects of non childbearing potential must meet at least 1 of the following criteria:

   1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
   2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
   3. Have medically confirmed ovarian failure.

   All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential and will be eligible with adequate contraceptive usage.

3. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

Subjects with any of the following characteristics/conditions will not be included in the study:

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. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
3. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
4. Any current evidence of untreated active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB).
5. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing
6. Benign ethnic (cyclic) neutropenia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OC only; Subjects will receive a single dose of an oral contraceptive during the first period of the study	Drug: Ethinyl estradiol (EE) and levonogestrel (LN); Single dose of Oral tablet containing 30 ug EE and 150 ug of LN; Other Names: Oral contraceptive (OC)
Experimental: PF-06650833 + OC; Subjects will receive PF-06650833 every day for 11 days and a single dose of an oral contraceptive on day 10.	Drug: Ethinyl estradiol (EE) and levonogestrel (LN); Single dose of Oral tablet containing 30 ug EE and 150 ug of LN; Other Names: Oral contraceptive (OC); Drug: PF-06650833; 400 mg by mouth (PO) Once daily (QD) for 11 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Ethinyl Estradiol	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for EE was determined using linear/Log trapezoidal method.	Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration for Levonorgestrel	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for LN was determined using linear/Log trapezoidal method.	Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2
Maximum Plasma Concentration (Cmax) for Ethinyl Estradiol	Cmax was defined as maximum plasma concentration. Cmax for EE was observed directly from data.	Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2
Maximum Plasma Concentration for Levonorgestrel	Cmas was defined as maximum plasma concentration. Cmax for LN was observed directly from data.	Predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36 and 48 hours post OC dose in Periods 1 and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Events	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	From the first dose up to 35 days after the last dose of study intervention
Number of Participants With Treatment Emergent Adverse Events by Severity	An AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. AEs are classified according to the severity in 3 categories. a) mild - AEs does not interfere with participant's usual function; b) moderate - AEs interferes to some extent with participant's usual function; c) severe - AEs interferes significantly with participant's usual function. Only those categories in which at least 1 participant had data were reported.	From the first dose up to 35 days after the last dose of study intervention
Number of Participants With Categorical Vital Signs Data of Potential Clinical Concern	Systolic blood pressure (BP), diastolic BP and supine pulse rate measurements meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: Systolic BP min. <90 mmHg; Systolic BP max. decrease ≥30 or max. increase ≥30; Diastolic BP min. <50 mmHg; Diastolic BP max. decrease ≥20 or max. increase ≥20; Supine pulse rate min. <40 bpm or max. >120 bpm.	Day 1 for Period 1 and Day 1, Day 10, Day 12 for Period 2
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern	Hematology (hemoglobin, hematocrit, erythrocytes [Ery.], Ery.mean corpuscular volume, Ery.mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); clinical chemistry (bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase); and urinalysis (pH, glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin, nitrite, leukocyte esterase, Ery., leukocytes, epithelial cells, casts and bacteria) tests were assessed. Only those categories, in which at least 1 participant had data were reported.	Day 10, Day 12 for Period 2

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, 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 8, 2021
• Primary Completion (Actual): December 16, 2021
• Study Completion (Actual): December 16, 2021

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Estradiol; Contraceptive Agents; Ethinyl Estradiol; Contraceptives, Oral
• Other Study ID Numbers: B7921026

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