Multiple Ascending Dose Study of TD-1439 in Healthy Adult and Elderly Subjects

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

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

Conditions
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Healthy Adults, Elderly 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 has 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: 80 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 |
| --- | --- | --- |
| The number of adverse events by severity, including changes in vital signs, physical examination, laboratory safety tests, and ECGs. |  | From Day 1 through end of study (Day 25) | 

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 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in plasma after multiple doses - time to peak plasma concentration (Tmax) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in plasma after multiple doses - time to last measurable concentration (Tlast) |  | Day 1 to 3 days after last dose (Day 17) | 
| 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 to 3 days after last dose (Day 17) | 
| 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 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in plasma after multiple doses - CL/F (oral plasma clearance) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in plasma after multiple doses - Vz/F (apparent volume of distribution during the terminal phase) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in plasma after multiple doses - t1/2 (half-life) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in urine after multiple doses - Ae (amount excreted in urine) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in urine after multiple doses - Fe (fraction of oral dose excreted in urine) |  | Day 1 to 3 days after last dose (Day 17) | 
| PK of TD-1439 in urine after multiple doses - Clr (renal clearance) |  | Day 1 to 3 days after last dose (Day 17) | 
| Pharmacodynamic assessments for plasma atrial natriuretic peptide (ANP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 17) | 
| Pharmacodynamic assessments for plasma cyclic guanosine monophosphate (cGMP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 17) | 
| Pharmacodynamic assessments for urine cyclic guanosine monophosphate (cGMP) concentrations |  | The day before dosing (Day -1) to 3 days after last dose (Day 17) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple ascending dose (MAD)