Single Dose Bioavailability and Ethnobridging PK Study in Healthy Subjects

NCT04587713 | Completed Phase 1 FDA Drug

• 1 other identifier: 0184
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, 2-part, open-label study. Part A will be a formulation bridging and food effect study in healthy adult subjects. Part B will be an assessment of pharmacokinetics (PK) in healthy adult Chinese subjects.

Conditions

Intestinal Disorder; Bowel Diseases, Inflammatory

Keywords

Healthy Caucasian Subjects; Healthy Chinese Subjects; Ethnobridging

Outcome Measures

Primary Outcomes (3)

• AUC0-t

  Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of TD-1473 in Plasma

  Predose and at prespecified time points up to 5 days after dosing on Day 1 of each period

• AUC0-inf

  Area under the concentration-time curve, from time 0 extrapolated to infinity (AUC0-inf) of TD-1473 in Plasma

  Predose and at prespecified time points up to 5 days after dosing on Day 1 of each period

• Cmax

  Maximum observed concentration (Cmax) of TD-1473 in Plasma

  Predose and at prespecified time points up to 5 days after dosing on Day 1 of each period

Secondary Outcomes (1)

• Adverse events

  Day 1 through Day 7 of each period

Study Arms (9)

Part A, Sequence 1

EXPERIMENTAL

Part A, Sequence 1 = Treatment (Tx) C, Tx A, Tx C, Tx A Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 2

EXPERIMENTAL

Part A, Sequence 2: Tx D, Tx B, Tx D, Tx B Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 3

EXPERIMENTAL

Part A, Sequence 3: Tx C, Tx A, Tx D, Tx B Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 4

EXPERIMENTAL

Part A, Sequence 4: Tx D, Tx B, Tx C, Tx A Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 5

EXPERIMENTAL

Part A, Sequence 5: Tx A, Tx C, Tx A, Tx C Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 6

EXPERIMENTAL

Part A, Sequence 6: Tx B, Tx D, Tx B, Tx D Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 7

EXPERIMENTAL

Part A, Sequence 7: Tx A, Tx C, Tx B, Tx D Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part A, Sequence 8

EXPERIMENTAL

Part A, Sequence 8: Tx B, Tx D, Tx A, Tx C Single oral dose of treatment on Day 1 of each period in a 4-way crossover design with a ≥10-day washout period between treatments

Drug: TD-1473 [Tablet A]; Drug: TD-1473 [Tablet B]

Part B,Treatment A

EXPERIMENTAL

Single oral dose of Treatment A on Day 1

Drug: TD-1473 [Tablet A]

Interventions

TD-1473 [Tablet A] DRUG

TD-1473 \[Tablet A\] (1 Tablet = Dose A) proposed commercial tablet formulation

Part A, Sequence 1; Part A, Sequence 2; Part A, Sequence 3; Part A, Sequence 4; Part A, Sequence 5; Part A, Sequence 6; Part A, Sequence 7; Part A, Sequence 8; Part B,Treatment A

TD-1473 [Tablet B] DRUG

TD-1473 \[Tablet B\] (2 Tablets = Dose A) current clinical tablet formulation

Part A, Sequence 1; Part A, Sequence 2; Part A, Sequence 3; Part A, Sequence 4; Part A, Sequence 5; Part A, Sequence 6; Part A, Sequence 7; Part A, Sequence 8

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a non-smoking male or female adult
• Subject (females) must be of non-childbearing potential or if of childbearing potential, subject must not be pregnant or breastfeeding, and must agree to use highly effective birth control and must not donate ova through 30 days after last dose of study drug.
• Subject (males) must agree to use contraception to prevent pregnancy/partner exposure and must not donate sperm through 30 days after last dose of study drug.
• Subject has a body mass index (BMI) 19 to 30 kg/m\^2, inclusive and weighs at least 50 kg
• Subject is healthy as determined by the Principal Investigator or designee based on medical history and physical examinations performed at Screening and Day -1 of Period 1
• Subject must be willing and able to comply with the study diet, willing to abstain from strenuous physical activity which could cause muscle aches or injury, including contact sports for a period of 48 hours prior to study and through follow-up visit.
• Subject must be willing and able to give and understand written informed consent, communicate well with the PI, and comply with the study procedures, requirements and restrictions
• Part B: subject was born in China, with 2 Chinese biological parents and 4 Chinese grandparents as confirmed by interview, has lived no longer than 10 years outside of China, and has had no significant change in lifestyle, including diet, since leaving China

You may not qualify if:

• Subject is planning to conceive a child during the study or within 1 month after the last dose of TD 1473
• Subject has evidence or history of clinically significant allergic disease, hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease
• Subject has history of venous thrombosis
• Subject has any clinically significant abnormalities in the results of laboratory evaluations, or liver function tests exceeding the upper limit of normal in the screening or pre-dose period
• Subject has creatinine clearance as calculated by Cockcroft-Gault formula \<90mL/min at screening or pre-dose period.
• Subject has any medical condition possibly affecting drug absorption
• Subject has history of lymphoma, leukemia, or other types of malignancy
• Subject previously participated in a study for TD 1473 and/or subject has previously taken tofacitinib or other JAK inhibitors.
• Subject participated in another clinical trial of an investigational drug (or medical device) within 30 days
• Subject is unwilling to abstain from ingestion of caffeine or xanthine-containing products
• Subject is unwilling to abstain from alcohol beginning 24 hours prior to study start
• Subject has history of alcoholism or drug abuse
• Female subject who is pregnant and/or lactating
• Subject has positive results at Screening for human immunodeficiency virus (HIV), hepatitis A virus (HAV) antibodies, hepatitis B virus antigen (HBsAg), hepatitis B core antibodies (HBcAb), or hepatitis C virus (HCV) antibody
• Subject has confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19)

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (2)

Theravance Biopharma Investigational Site

Cypress, California, 90630, United States

Location

Theravance Biopharma Investigational Site

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Conditions

Intestinal Diseases; Inflammatory Bowel Diseases

Interventions

izencitinib

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis

Study Officials

• Study Director

  Theravance Biopharma

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 14, 2020
• Study Start: October 16, 2020
• Primary Completion: December 24, 2020
• Study Completion: December 27, 2020
• Last Updated: April 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)