A Phase 1, Multiple Intravenous Dose Study to Examine Safety, Tolerability, and PK of Intravenous TD-8954, a 5-HT4 Receptor Agonist, in Healthy Subjects

Phase 1

Terminated

• Conditions: Gastrointestinal Motility Disorder
• Interventions: Drug: Placebo - saline; Drug: TD-8954

• Registration Number: NCT01644240
• Lead Sponsor: Theravance Biopharma

Brief Summary

This is a single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics (PK) of repeated IV doses of TD-8954 in healthy adults 18 to 45 years of age and healthy elderly subjects 65 to 85 years old. A healthy elderly subject population is included to evaluate the safety, tolerability, and PK of TD-8954 IV. Pharmacodynamic effects on bowel movements will also be evaluated. Screening for all cohorts will be conducted within 21 days before the first dose.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-13
• Study First Submitted QC: 2012-07-18
• Study First Posted: 2012-07-19
• Study Start: 2012-09
• Primary Completion: 2012-11
• Study Completion: 2012-12
• Results First Submitted: 2016-12-21
• Status Verified: 2017-04
• Results First Submitted QC: 2017-04-18
• Last Update Submitted: 2017-04-18
• Results First Posted: 2017-08-02
• Last Update Posted: 2017-08-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. For Cohorts 1: adult males and females age 18 to 45 years, inclusive; for Cohorts 2 and 3, adult males and females 65 to 85 years of age, inclusive; for Cohort 4, adult males and females 18 to 45 or 65 to 85 years of age, inclusive.
2. Body mass index (BMI)between 18 to 36 kg/m2, inclusive.
3. Average frequency of ≥ 3 bowel movements per week.

Exclusion Criteria

1. Persistent symptoms of functional GI disorder (such as irritable bowel syndrome, functional constipation, functional dyspepsia, or other symptom-based GI disorders unexplained by a pathologically based disorder) during the 6 months prior to screening, including a history of major surgery of the GI tract, excluding cholecystectomy and appendectomy.
2. History or presence of clinically significant respiratory, GI, renal, hepatic, endocrine, hematological, neurological (including chronic headache, current or prior psychiatric disease/condition, stroke), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, or dermatological disorders. Subjects with mild, chronic, stable disease (e.g., controlled hypertension, controlled hypercholesterolemia, non insulin-dependent diabetes, osteoarthritis) may be enrolled if the condition is well controlled and not anticipated to interfere with the objectives of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo - saline	-
TD-8954 Dose 2	TD-8954	-
TD-8954 Dose 1	TD-8954	-

Primary Outcome Measures

Name	Time	Method
Vss	Day 5	Apparent volume of distribution at steady state
Cmax	Day 5	Maximum plasma concentration
Tmax	Day 5	Time to reach maximum plasma concentration.
t½	Day 5	Time to 50% plasma concentration
AUC0-24	Day 5	Area under the plasma concentration time curve 24 hours following the last dose.
AUC0-∞	Day 5	Area under the plasma concentration time curve from 0 to infinity.
AUCtau	Day 5	Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.
CLss	Day 5	Apparent clearance
Plasma CL	Day 1	Plasma clearance
Plasma Vz	Day 1	Volume of distribution

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Adverse Events	1 week

Trial Locations

Locations (1)

Miami Research Associates; 🇺🇸 Miami, Florida, United States