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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-06650833
* Drug: Ethinyl estradiol (EE) and levonogestrel (LN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study: Healthy female subjects Female subjects of non childbearing potential must meet at least 1 of the following criteria: 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; Have undergone a documented hysterectomy and/or bilateral oophorectomy; 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. 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: 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). 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). Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). Any current evidence of untreated active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB). History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing Benign ethnic (cyclic) neutropenia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |