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

Phase 1
Completed
Conditions
Healthy Adults, Elderly Subjects
Interventions
Drug: Placebo
Registration Number
NCT02709928
Lead Sponsor
Theravance Biopharma
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TD-0714TD-0714Capsule formulation
PlaceboPlaceboCapsule formulation
Primary Outcome Measures
NameTimeMethod
Safety of TD-0714 by assessing the number and severity of adverse events, including changes in vital signs, physical examination, laboratory safety tests, and ECGsFrom Day 1 through end of study (Day 25)
Secondary Outcome Measures
NameTimeMethod
PK of TD-0714 in plasma after multiple doses - time to peak plasma concentration (Tmax)Day 1 through Day 17
Pharmacodynamic assessments for plasma atrial natriuretic peptide (ANP) concentrationsThe day before dosing (Day -1) to 3 days after last dose (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
Pharmacodynamic assessments for urine cyclic guanosine monophosphate (cGMP) concentrationsThe day before dosing (Day -1) to 3 days after last dose (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 urine after multiple doses - Clr (renal clearance)Day 1 through 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 last measurable concentration (Tlast)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
Pharmacodynamic assessments for plasma cyclic guanosine monophosphate (cGMP) concentrationsThe day before dosing (Day -1) to 3 days after last dose (Day 17)
PK of TD-0714 in urine after multiple doses - Fe (fraction of oral dose excreted in urine)Day 1 through Day 17
Pharmacodynamic assessments for urine atrial natriuretic peptide (ANP) concentrationsThe day before dosing (Day -1) to 3 days after last dose (Day 17)

Trial Locations

Locations (1)

Celerion

🇺🇸

Lincoln, Nebraska, United States

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