Single Ascending Dose Study of TD-1439 in Healthy Subjects

Study Overview
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Brief Summary
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Single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1439 in healthy subjects

Official Title
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A Phase 1, Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TD-1439 in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: TD-1439
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) 18 to 32 kg/m2 inclusive Women of child bearing potential must have a negative pregnancy test and either abstain from sex or use highly effective methods of birth control Women of non-childbearing potential are at least 2 years postmenopausal or are surgically sterile Males must abstain from sex or use highly effective methods of birth control Negative for HIV, and Hepatitis A, B, and C Exclusion Criteria: Female subjects who are pregnant, lactating, breastfeeding or planning to become pregnant during the study. Subjects with a history of angioedema. Subject has evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dosing), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Subject has acute illness (gastrointestinal, infection [e.g., influenza] or known inflammatory process) Subject bradycardia Subject has hypertension Subjects has orthostatic hypotension Subjects has orthostatic tachycardia Subject has a known personal or family history of congenital long QT syndrome or known family history of sudden death. Subject has donated blood or blood components or has had blood loss exceeding 400 mL within the 90 days prior to Screening. Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-1439<br>Capsule formulation | Drug: TD-1439<br> <br> |
| Placebo Comparator: Placebo<br>Capsule formulation | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of TD-1439 by assessing the number and severity of adverse events, including changes in vital signs, physical examination, laboratory safety tests, and ECGs |  | From Day 1 through end of study (Day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of TD-1439 in plasma after multiple doses - peak plasma concentration (Cmax) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - time to peak plasma concentration (Tmax) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - time to last measurable concentration (Tlast) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - area under the plasma concentration vs. time curve from time zero to the last quantifiable concentration (AUC0-t) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - area under the plasma concentration vs. time curve from time zero to 24 hours postdose (AUC0-24) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - CL/F (oral plasma clearance) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - Vz/F (apparent volume of distribution during the terminal phase) |  | Day 1 through Day 10 | 
| PK of TD-1439 in plasma after multiple doses - t1/2 (half-life) |  | Day 1 through Day 10 | 
| PK of TD-1439 in urine after multiple doses - Ae (amount excreted in urine) |  | Day 1 through Day 10 | 
| PK of TD-1439 in urine after multiple doses - Fe (fraction of oral dose excreted in urine) |  | Day 1 through Day 10 | 
| PK of TD-1439 in urine after multiple doses - Clr (renal clearance) |  | Day 1 through Day 10 | 
| Pharmacodynamic assessments for plasma atrial natriuretic peptide (ANP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 4) | 
| Pharmacodynamic assessments for urine atrial natriuretic peptide (ANP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 4) | 
| Pharmacodynamic assessments for plasma cyclic guanosine monophosphate (cGMP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 4) | 
| Pharmacodynamic assessments for urine cyclic guanosine monophosphate (cGMP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single ascending dose