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

Sponsor

Theravance Biopharma (Industry)

Overall Status

Completed

CT.gov ID

NCT03432793

Collaborator

(none)

Enrollment

Location

Arms

1.7

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Drug Drug Interaction (DDI)	Drug: TD-9855 Drug: Fluvoxamine Drug: Itraconazole Drug: Caffeine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 28, 2018

Actual Primary Completion Date :

Apr 21, 2018

Actual Study Completion Date :

Apr 21, 2018

Arms and Interventions

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: Itraconazole oral tablet solution, QD Drug: Caffeine oral solution, single dose

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: Itraconazole

oral tablet solution, QD

Drug: Caffeine

oral solution, single dose

Outcome Measures

Primary Outcome Measures

Change in TD-9855 plasma exposure when administered with itraconazole or fluvoxamine [Day 9 and Day 24]

Secondary Outcome Measures

Correlation between caffeine PK disposition and TD-9855 plasma exposure [Day 9 and Day 24]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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