Tofacitinib Citrate Topical Gel 3.2% FDA BA Bridging Study

NCT04468425 | Completed Phase 1 FDA Drug

• 1 other identifier: AC-1101-PK-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, single center, open-label, fixed sequence, two-period pharmacokinetic (PK) study to evaluate the safety and relative systemic bioavailability of topical and oral tofacitinib formulations in approximately 14 healthy subjects. Participants will receive a single oral dose of tofacitinib 5 mg tablet in Period 1 of the study followed by a 7-day washout period. In Period 2, participants will receive repeat administration of Tofacitinib Citrate Topical Gel 3.2% BID for 14 days.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (7)

• Maximum Plasma Concentration [Cmax] of tofacitinib from single oral dosing in Period 1

  Day 1

• Area Under Curve [AUC] of tofacitinib from single oral dosing in Period 1

  Day 1

• Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2

  Day 8

• Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2

  Day 8

• Maximum Plasma Concentration [Cmax] of tofacitinib from repeat topical dosing in Period 2

  Day 21

• Area Under Curve [AUC] of tofacitinib from repeat topical dosing in Period 2

  Day 21

• Safety and tolerability of Tofacitinib Citrate Topical Gel 3.2% as assessed by treatment-emergent adverse events and Dermal Reaction Scoring, respectively.

  Day 24

Study Arms (1)

Pharmacokinetic Study

EXPERIMENTAL

Period 1 (Day 1) and 2 (Day 8 - Day 21) separated by 7-day washout period. Period 1: A single 5 mg tofacitinib tablet will be administered orally on Day 1. Period 2: Repeat dosing of Tofacitinib Citrate Topical Gel 3.2% to approximately 10% BSA in the morning of Day 8 and twice daily from Day 9 to Day 20 with the last dose in the morning of Day 21.

Drug: Tofacitinib Citrate

Interventions

Tofacitinib Citrate DRUG

Period 1: Xelijanz® 5 mg tablet (tofacitinib citrate) for single oral dosing. Period 2: Tofacitinib Citrate Topical Gel 3.2% for repeat topical dosing BID for 14 days.

Pharmacokinetic Study

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, smoker (no more than 25 cigarettes or equivalent daily) or non-smoker, ≥18 and ≤60 years of age, with BMI \>18.5 and \<30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Healthy as defined by:
• The absence of clinically significant history of dermatological, neurological, endocrine, cardiovascular, respiratory, hematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration:
• Intra-uterine contraceptive device without hormone release system placed at least 4 weeks prior to study drug administration;
• Male condom with intravaginally applied spermicide started at least 21 days prior to study drug administration;
• Sterile male partner (vasectomized since at least 6 months).
• Absence of excessive body hair at the topical application site, or willing to have excess body hair removed prior to dosing.
• Capable of consent.

You may not qualify if:

• Presence of any clinically significant abnormality at physical examination, clinically significant abnormal laboratory assessment or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
• Positive urine drug screen or alcohol breath test at screening.
• History of allergic reactions to tofacitinib or other related drugs, or to any excipient in the formulation.
• Positive pregnancy test at screening.
• Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.
• History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week \[1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]).
• History of significant drug abuse within 1 year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the pharmacokinetic profile of the study drug or subject safety e.g. topical drug products without significant systemic absorption (not including topical drug products administered to the gel application site):
• Prescription medications within 14 days prior to the first dosing;
• Over-the-counter products and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing, with the exception of the occasional use of acetaminophen (up to 2 g daily);
• Depot injection or implant of any drug within 3 months prior to the first dosing;
• Any drugs known to induce or inhibit hepatic drug metabolism via the CYP3A4 and CYP2C19 enzymes within 30 days prior to first dose;
• Examples of inducers for CYP3A4 include barbiturates, carbamazepine, phenytoin, glucocorticoids, St. John's wort, etc.
• Examples of inhibitors for CYP3A4 include HIV antivirals, clarithromycin, ciprofloxacin, gestodene, etc.

Sponsors & Collaborators

• TWi Biotechnology, Inc.: lead

Study Sites (1)

Syneos Health Facility

Québec, Canada

Location

MeSH Terms

Interventions

tofacitinib

Study Design

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

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 13, 2020
• Study Start: October 14, 2020
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: November 29, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)