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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastrointestinal Motility Disorder

Intervention / Treatment
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* Drug: TD-8954
* Drug: Placebo - saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-8954 Dose 1<br> | Drug: TD-8954<br>* Intravenous infusion<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo - saline<br>* Intravenous infusion<br>|
| Experimental: TD-8954 Dose 2<br> | Drug: TD-8954<br>* Intravenous infusion<br>|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Events |  | 1 week |