A STUDY TO ESTIMATE THE EFFECT OF PF-06651600 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, randomized, 2 way crossover, multiple dose, open label study of the effect of multiple dose PF-06651600 on single dose OC PK in healthy female subjects. Subjects will be randomized to 1 of 2 treatment sequences.

Official Title
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A PHASE 1, RANDOMIZED, OPEN LABEL, 2-WAY CROSSOVER STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSE PF-06651600 ON THE PHARMACOKINETICS OF SINGLE DOSE ORAL CONTRACEPTIVE STEROIDS IN HEALTHY FEMALE SUBJECTS

Conditions
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Healthy Females

Intervention / Treatment
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* Drug: PF-06651600
* 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 of non childbearing potential 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 are not eligible for this study. Body mass index (BMI) of 17.5 to 35 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 drug abuse with less than 6 months of abstinence prior to the baseline visit. History of regular alcohol consumption exceeding 7 drinks/week for female subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening. Any medical reason which would contraindicate the administration of oral contraceptives (as per the label) or history of discontinued use of oral contraceptives due to medical reasons. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency. Subjects who have a malignancy or a history of malignancy, with the exception of adequately treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence 1<br>Treatment sequence 1 will receive a single dose of an oral contraceptive during the first period of the study (period 1) and then continue to the second period (Period 2) of the study where they will receive PF-06651600 every day for 11 days and a single dose of an oral contraceptive towards the end of the period. | Drug: PF-06651600<br>* 200 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;|
| Experimental: Treatment Sequence 2<br>Treatment sequence 2 will receive PF-06651600 every day for 11 days during the first period of the study (period 1) and a single dose of an oral contraceptive towards the end of this period. After completion of Period 1, there will be a washout period of at least 10 days before starting the second period of the study (period 2). During period 2, a single dose of an oral contraceptive will be received. | Drug: PF-06651600<br>* 200 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;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for EE | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | 0 (pre-dose),1, 1.5. 2,4,6,8,12,24 and 48 hours post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for LN | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | 0 (pre-dose), 1, 1.5, 2, 4, 6, 8, 12, 24 and 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) |  | Baseline (Day 0) up to 28 days after last dose of study drug | 
| Number of Adverse Events by Severity |  | Baseline up to 28 days after last dose | 
| Number of Participants With Categorical Vital Signs Data |  | Baseline through study completion, approximately 23 days. | 
| Number of Participants With Change From Baseline in Laboratory Tests Results |  | Baseline through study completion, approximately 23 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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female, post-menopausal, healthy, oral contraceptive