Single Ascending Dose Study of TD-0714 in Healthy Subjects

A Phase 1, Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TD-0714 in Healthy Subjects

Single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-0714 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: TD-0714; Drug: Placebo Comparator

• Study Type: Interventional
• Enrollment (Actual): 56
• 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: No
• 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 Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TD-0714; One time dosing in capsule formulation	Drug: TD-0714; One time dosing in capsule formulation
Placebo Comparator: Placebo; Placebo comparator one time dosing in capsule formulation	Drug: Placebo Comparator; One time dosing in capsule formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of TD-0714 by assessing the number, severity and type of adverse events, including changes in vital signs, physical and neurological examinations, 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-0714 in plasma after a single-dose (SD): peak plasma concentration (Cmax)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: time to peak plasma concentration (Tmax)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: time to last measurable concentration (Tlast)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: area under the plasma concentration vs. time curve from time zero to the last quantifiable concentration (AUC0-t)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: area under the plasma concentration vs. time curve from time zero to 24 hours postdose (AUC0-24)	The day before dosing (Day -1) to the day after dosing (Day 2)
PK of TD-0714 in plasma after a SD: area under the plasma concentration vs. time curve from time zero to infinity (AUC0-∞)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: CL/F (oral plasma clearance)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: Vz/F (apparent volume of distribution during the terminal phase)	Day 1 through end of study (Day 10)
PK of TD-0714 in plasma after a SD: t1/2 (half-life)	Day 1 through end of study (Day 10)
PK of TD-0714 in urine after a SD: Ae (amount excreted in urine)	Day 1 through end of study (Day 10)
PK of TD-0714 in urine after a SD: Fe (fraction of oral dose excreted in urine)	Day 1 through end of study (Day 10)
PK of TD-0714 in urine after a SD: Clr (renal clearance)	Day 1 through end of study (Day 10)

Other Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics assessments for plasma atrial natriuretic peptide (ANP) concentrations	The day before dosing (Day -1) to the day after dosing (Day 2)
Pharmacodynamics assessments for urine atrial natriuretic peptide (ANP) concentrations	The day before dosing (Day -1) to the day after dosing (Day 2)
Pharmacodynamics assessments for plasma cyclic guanosine monophosphate (cGMP) concentrations	The day before dosing (Day -1) to the day after dosing (Day 2)
Pharmacodynamics assessments for urine cyclic guanosine monophosphate (cGMP) concentrations	The day before dosing (Day -1) to the day after dosing (Day 2)

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: December 21, 2015
• First Posted (Estimate): December 24, 2015

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: volunteers; Phase 1; first-in-human; Single ascending dose; TD-0714
• Other Study ID Numbers: 0139