Food-effect, Drug-Drug Interaction (DDI), and Formulation Bridging Study

A Phase 1, Open-Label, 2-Cohort Study to Assess the Single Dose Pharmacokinetics of Two Formulations of TD-1473 and to Assess the Effect of a High-Fat Meal and Itraconazole on the Pharmacokinetics of TD-1473 in Healthy Subjects

This is a Phase 1, open-label, 2-cohort, food-effect, DDI, and formulation bridging study.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Drug: TD-1473; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between 18 to 55 years old
• Male subjects must abstain from sexual intercourse or use a highly effective method of birth control
• Women of child bearing potential must have a negative pregnancy test and either abstain from sex or use a highly effective method of birth control
• Body Mass Index (BMI) 18 to 32 kg/m2
• Willing and able to give informed consent
• Additional inclusion criteria apply

Exclusion Criteria:

• Planning to conceive a child during the study or within 2 months after the last dose of study drug
• Is positive for hepatitis A, B or C, and/or HIV
• Has clinically significant abnormalities in baseline laboratory evaluations
• Subject has a clinically significant abnormal electrocardiogram (ECG)
• Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another trial of an investigational drug (or medical device)
• Additional exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-1473 formulation bridging & food effect; Subjects will receive, on Day 1 of each period, a single 100 mg oral dose of the tablet formulation of TD-1473 in the fed or fasted state, or the PIC formulation of TD-1473 in the fasted state, as part of a 3-period, crossover design.	Drug: TD-1473; oral capsule/tablet, QD
Experimental: TD-1473 with Itraconazole; Subjects will receive a single 100 mg oral dose of the tablet formulation of TD-1473 in the fasted state on Day 1 of Period 1. In Period 2, subjects will receive, in the fasted state, single oral doses of 200 mg itraconazole solution on Days -4 through 7 for a total of 11 days, with a single 100 mg oral dose of the tablet formulation of TD-1473 co-administered on Day 1.	Drug: TD-1473; oral capsule/tablet, QD; Drug: Itraconazole; oral solution, QD
Experimental: TD-1473 without Itraconazole; Subjects will receive a single 100 mg oral dose of the tablet formulation of TD-1473 in the fasted state on Day 1 of Period 1.	Drug: TD-1473; oral capsule/tablet, QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) in Plasma	Up to 8 days post-dose
Time to maximum observed concentration (tmax) in Plasma	Up to 8 days post-dose
Area under the concentration-time curve from hour 0 to the last measurable concentration (AUC0-last) in Plasma	Up to 8 days post-dose
Area under the concentration-time curve extrapolated to infinity (AUC0-inf) in Plasma	Up to 8 days post-dose
Apparent terminal elimination half-life (t1/2) in Plasma	Up to 8 days post-dose
Apparent clearance (Cl/F) in Plasma	Up to 8 days post-dose
Apparent volume of distribution (Vz/F) in Plasma	Up to 8 days post-dose

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2018
• Primary Completion (Actual): July 15, 2018
• Study Completion (Actual): July 15, 2018

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 13, 2018

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; IBS; Inflammatory Bowel Disease; healthy volunteers; IBD; drug-drug interaction; CYP3A; itraconazole; P-gp
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 0174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No