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

NCT01644240 | Terminated Phase 1 Results

• 1 other identifier: 0095
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Motility Disorder

Outcome Measures

Primary Outcomes (16)

• 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 Outcomes (1)

• Number of Subjects With Adverse Events

  1 week

Study Arms (3)

TD-8954 Dose 1

EXPERIMENTAL

Drug: TD-8954

Placebo

PLACEBO COMPARATOR

Drug: Placebo - saline

TD-8954 Dose 2

EXPERIMENTAL

Drug: TD-8954

Interventions

TD-8954 DRUG

Intravenous infusion

TD-8954 Dose 1; TD-8954 Dose 2

Placebo - saline DRUG

Intravenous infusion

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Body mass index (BMI)between 18 to 36 kg/m2, inclusive.
• Average frequency of ≥ 3 bowel movements per week.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (1)

Miami Research Associates

Miami, Florida, 33143, United States

Location

MeSH Terms

Interventions

4-((4-((2-isopropyl-1H-benzoimidazole-4-carbonyl)amino)methyl)piperidin-1-ylmethyl)piperidine-1-carboxylic acid methyl ester

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Brett Haumann, SVP, Clinical Development
• Organization: Theravance Biopharma US, Inc.

BHaumann@theravance.com

650-808-6000

Study Officials

• Brett Haumann, SVP, Clinical Development

  Theravance Biopharma, US, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2012
• First Posted: July 19, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 2, 2017
• Results First Posted: August 2, 2017

Record last verified: 2017-04

Locations

US (1)