Drug-Drug Interaction (DDI) Study for TD-9855

A Phase 1, Fixed-Sequence, Open-Label Drug-Drug Interaction Study to Assess the Effect of Fluvoxamine (CYP1A2 Inhibitor), Cigarette Smoking (CYP1A2 Inducer) and Itraconazole (CYP3A4 Inhibitor) on the Pharmacokinetics of TD-9855 in Healthy Subjects

This study is designed to assess the effect of fluvoxamine, itraconazole and smoking on the PK disposition of multiple doses TD-9855 in healthy male subjects. The study will also assess the relationship between caffeine PK and TD-9855 PK disposition in healthy male smokers and non-smokers.

Study Overview

• Status: Completed
• Conditions: Drug Drug Interaction (DDI)
• Intervention / Treatment: Drug: TD-9855; Drug: Fluvoxamine; Drug: Caffeine; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 41
• 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: Male

Description

Inclusion Criteria:

• Willing and able to give written, signed informed consent
• Male subjects 19 to 55 years of age (inclusive)
• Body mass index 19 to 32 kg/m2 (inclusive), and weigh at least 55 kg
• No clinically important abnormal physical findings as determined by the Principal Investigator (PI) at the screening and Day -1 examinations
• Negative for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) antibody at screening.
• No clinically important laboratory abnormalities as determined by the PI
• Ability to communicate effectively with the Investigator and to comply with all study requirements, restrictions, and direction of the clinic staff
• Male subjects must abstain from sexual intercourse or use a highly effective method of birth control
• Male smokers: Subjects who self-report to have smoked > 9 cigarettes per day for at least 6 month prior to screening as confirmed by urine cotinine test at screening and Day -1.
• Male smokers: Subjects must be willing to continue consistent use of their tobacco products throughout the study.
• Additional inclusion criteria apply

Exclusion Criteria:

• Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) antibody at screening.
• History or presence of clinically significant respiratory, gastrointestinal, renal, hepatic, hematologic, neurologic (including history of seizure and insomnia), cardiovascular (including postural orthostatic hypotension or tachycardia), psychiatric (including depression and known addictive disorders), musculoskeletal, genitourinary (including urinary retention), immunologic, or dermatologic disorder.
• Any other condition that, in the opinion of the PI, would confound or interfere with study participation; evaluation of safety, tolerability, or PK of the investigational drug; or prevent compliance with the study protocol
• Any history of suicide attempts/ideation or current suicidal ideation.
• Have participated in another clinical trial of an investigational drug (or medical device) within 30 days (or 5 half-lives of the investigational drug if longer than 30 days) prior to Screening, or are currently participating in another trial of an investigational drug (or medical device), or intending to participate in another trial of an investigational drug (or medical device) before completion of all scheduled safety evaluations in this trial
• Additional inclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-9855 + Fluvoxamine + Caffeine; Male smokers will receive TD-9855, fluvoxamine, and caffeine	Drug: TD-9855; oral tablet, QD; Drug: Fluvoxamine; oral tablet, QD; Drug: Caffeine; oral solution, single dose
Experimental: TD-9855 + Itraconazole + Caffeine; Male non-smokers will receive TD-9855, itraconazole, and caffeine	Drug: TD-9855; oral tablet, QD; Drug: Caffeine; oral solution, single dose; Drug: Itraconazole; oral tablet solution, QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in TD-9855 plasma exposure when administered with itraconazole or fluvoxamine	Day 9 and Day 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between caffeine PK disposition and TD-9855 plasma exposure	Correlation co-efficient will be calculated between caffeine/paraxanthine ratio at 4hr after caffeine dose and TD-9855 plasma AUC on Day 9 and Day 24.	Day 9 and Day 24

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): April 21, 2018
• Study Completion (Actual): April 21, 2018

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 14, 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: Smoking; Itraconazole; Caffeine; CYP3A4; Fluvoxamine; DDI; TD-9855; CYP1A2
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Itraconazole; Caffeine; Fluvoxamine
• Other Study ID Numbers: 0172

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