Multiple Ascending Dose Study of TD-0714 in Healthy and Elderly Subjects

A Phase 1, Double-blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TD-0714 in Healthy Adult and Elderly Subjects

Multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-0714 in healthy adult and elderly subjects

Study Overview

• Status: Completed
• Conditions: Healthy Adults, Elderly Subjects
• Intervention / Treatment: Drug: Placebo; Drug: TD-0714

• Study Type: Interventional
• Enrollment (Actual): 50
• 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 80 years (Adult, Older 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 Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Capsule formulation	Drug: Placebo
Experimental: TD-0714; Capsule formulation	Drug: TD-0714

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of TD-0714 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 25)

Secondary Outcome Measures

Outcome Measure	Time Frame
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)
Pharmacokinetics (PK) of TD-0714 in plasma after multiple doses - peak plasma concentration (Cmax)	Day 1 through Day 17
PK of TD-0714 in plasma after multiple doses - time to peak plasma concentration (Tmax)	Day 1 through Day 17
PK of TD-0714 in plasma after multiple doses - time to last measurable concentration (Tlast)	Day 1 through Day 17
PK of TD-0714 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 17
PK of TD-0714 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 17
PK of TD-0714 in plasma after multiple doses - CL/F (oral plasma clearance)	Day 1 through Day 17
PK of TD-0714 in plasma after multiple doses - Vz/F (apparent volume of distribution during the terminal phase)	Day 1 through Day 17
PK of TD-0714 in plasma after multiple doses - t1/2 (half-life)	Day 1 through Day 17
PK of TD-0714 in urine after multiple doses - Ae (amount excreted in urine)	Day 1 through Day 17
PK of TD-0714 in urine after multiple doses - Fe (fraction of oral dose excreted in urine)	Day 1 through Day 17
PK of TD-0714 in urine after multiple doses - Clr (renal clearance)	Day 1 through Day 17
Pharmacodynamic assessments for urine atrial natriuretic peptide (ANP) concentrations	The day before dosing (Day -1) to 3 days after last dose (Day 17)

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 7, 2016
• First Submitted That Met QC Criteria: March 10, 2016
• First Posted (Estimate): March 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: Multiple ascending dose
• Other Study ID Numbers: 0142

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO