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

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Intravenous Dose Study to Examine the Safety, Tolerability, and Pharmacokinetics of Intravenous TD-8954, a 5-HT4 Receptor Agonist, in Healthy Subjects

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.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Motility Disorder
• Intervention / Treatment: Drug: TD-8954; Drug: Placebo - saline

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo - saline; Intravenous infusion
Experimental: TD-8954 Dose 1	Drug: TD-8954; Intravenous infusion
Experimental: TD-8954 Dose 2	Drug: TD-8954; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Subjects With Adverse Events	1 week

Collaborators and Investigators

• Sponsor: Theravance Biopharma
• Investigators: Study Director: Brett Haumann, SVP, Clinical Development, Theravance Biopharma, US, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 13, 2012
• First Submitted That Met QC Criteria: July 18, 2012
• First Posted (Estimate): July 19, 2012

Study Record Updates

• Last Update Posted (Actual): August 2, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 0095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided