A Study to Determine the Effects of PF-04965842 on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Subjects

NCT03662516 | Completed Phase 1 FDA Drug

• 1 other identifier: B7451016
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, 2 way crossover, open-label study of the effect of multiple-dose PF 04965842 on single-dose OC PK in healthy female subjects. Subjects will be randomized to 1 of 2 treatment sequences. A total of 16 healthy female subjects (8 in each treatment sequence) will be enrolled in the study. Each treatment sequence will consist of 2 periods.

Conditions

Healthy Females

Keywords

PF-04965842

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (4)

• Laboratory tests

  Baseline through study completion, approximately 15 days for sequence 1 and 25 days for sequence 2.

• Adverse Events (AEs)

  Baseline (Day 0) up to 28 days after last dose of study drug

• Vital signs

  Baseline through study completion, approximately 15 days for sequence 1 and 25 days for sequence 2.

• 12-lead ECGs

  Day 1 and Day 12 of PF-04965842 and OC co-administration period.

Study Arms (2)

Sequence 1

OTHER

In Treatment Sequence 1, Period 1 Day 1, subjects will be dosed with a single administration of OC in the form of 1 PORTIA (EE and LN) or equivalent tablet, orally. OC (EE and LN) PK will then be assessed at pre dose and over 48 hours after OC dosing. Period 1 will be immediately followed by Period 2 with no washout. The 48 hours post-OC dose PK sample for Period 1 must be collected prior to receiving the first dose of PF 04965842 in Period 2. In Period 2, subjects will be dosed with 200 mg PF 04965842 PO QD for 9 days followed by administration of a single dose of OC oral tablet immediately after administration of a 200 mg dose of PF-04965842 on the morning of Day 10. OC PK in Period 2 will be assessed at pre dose and over 48 hours after OC dosing. Dosing with 200 mg PF 04965842 PO QD will continue until Day 11.

Drug: PF-04965842; Drug: Ethinyl estradiol (EE) and levonorgestrel (LN)

Sequence 2

OTHER

In Treatment Sequence 2, Period 1, subjects will be dosed with 200 mg PF 04965842 PO QD for 9 days followed by administration of a single dose of OC oral tablet immediately after administration of a 200 mg dose of PF-04965842 on the morning of Day 10. OC PK will be assessed at pre dose and over 48 hours following OC dosing. Dosing with 200 mg PF 04965842 PO QD will continue until Day 11. Subjects will then undergo a washout period of at least 10 days (Day -1 of Period 2 starts 10 days after Day 12 of Period 1). In Period 2 subjects will be dosed with a single OC administration on Day 1. OC PK will then be assessed at pre dose and over 48 hours after OC dose.

Drug: PF-04965842; Drug: Ethinyl estradiol (EE) and levonorgestrel (LN)

Interventions

PF-04965842 DRUG

Orally bioavailable small molecule that selectively inhibits JAK 1 by blocking the adenosine triphosphate (ATP) binding site.

Also known as: JAK 1 inhibitor

Sequence 1; Sequence 2

Ethinyl estradiol (EE) and levonorgestrel (LN) DRUG

Single dose of Oral tablet containing 30 ug EE and 150 ug of LN

Also known as: Oral contraceptive

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Healthy female subjects of both childbearing and non-childbearing potential.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy female subjects of both childbearing and non-childbearing potential 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 measurement, 12 lead ECG, or clinical laboratory tests.
• 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; 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.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Evidence of acute exacerbation of dermatological condition (eg, AD or psoriasis) or visible rash present during physical examination.
• Subjects, who according to the product label for OC, would be at increased risk if dosed with OC.
• Based on PORTIA product label, combination OCs should not be used in women with any of the following conditions:
• Thrombophlebitis or thromboembolic disorders.
• A past history of deep-vein thrombophlebitis or thromboembolic disorders.
• Cerebral-vascular or coronary artery disease.
• Thrombogenic valvulopathies.
• Thrombogenic rhythm disorders.
• Diabetes mellitus with vascular involvement.
• Uncontrolled hypertension.
• Known or suspected carcinoma of the breast.
• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia.
• Undiagnosed abnormal genital bleeding.
• Cholestatic jaundice of pregnancy or jaundice with prior pill use.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (1)

• Wang X, Dowty ME, Tripathy S, Le VH, Huh Y, Curto M, Winton JA, O'Gorman MT, Chan G, Malhotra BK. Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals. Eur J Drug Metab Pharmacokinet. 2024 May;49(3):367-381. doi: 10.1007/s13318-024-00893-5. Epub 2024 Mar 30.

  PMID: 38554232 DERIVED

Related Links

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

MeSH Terms

Interventions

abrocitinib; Ethinyl Estradiol; Levonorgestrel; Contraceptives, Oral

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norgestrel; Norpregnenes; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Natural log transformed AUCinf, AUClast, and Cmax of EE and LN will be analyzed separately using a mixed effect model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Estimates of the adjusted mean differences (Test Reference) and corresponding 90% CIs will be obtained from the model. The adjusted mean differences and 90% CIs for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. OC (EE and LN) alone will be the Reference treatment, while the OC (EE and LN) coadministered with PF 04965842 will be the Test treatment. The absent of an effect of PF 04965842 on OC (EE and LN) will be concluded if the lower bound of 90% confidence interval for the ratio of adjusted geometric mean for AUCinf is ≥80%.

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: September 7, 2018
• Study Start: September 26, 2018
• Primary Completion: January 19, 2019
• Study Completion: January 19, 2019
• Last Updated: March 23, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)