Single Ascending Dose Study of TD-1439 in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Placebo; Drug: TD-1439

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TD-1439; Capsule formulation	Drug: TD-1439
PLACEBO_COMPARATOR: Placebo; Capsule formulation	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (ESTIMATE): September 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Single ascending dose
• Other Study ID Numbers: 0147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.