Clinical trial NCT02639078: Single Ascending Dose Study of TD-0714 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Single ascending dose
volunteers
Phase 1
first-in-human
TD-0714
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
First posted: 2015-12-24
Enrollment: 56
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: From Day 1 through end of study (Day 10)
Secondary outcomes:
measure: Pharmacokinetics (PK) of TD-0714 in plasma after a single-dose (SD): peak plasma concentration (Cmax)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in plasma after a SD: time to peak plasma concentration (Tmax)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in plasma after a SD: time to last measurable concentration (Tlast)
timeFrame: Day 1 through end of study (Day 10)
measure: 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)
timeFrame: Day 1 through end of study (Day 10)
measure: 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)
timeFrame: The day before dosing (Day -1) to the day after dosing (Day 2)
measure: PK of TD-0714 in plasma after a SD: area under the plasma concentration vs. time curve from time zero to infinity (AUC0-∞)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in plasma after a SD: CL/F (oral plasma clearance)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in plasma after a SD: Vz/F (apparent volume of distribution during the terminal phase)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in plasma after a SD: t1/2 (half-life)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in urine after a SD: Ae (amount excreted in urine)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in urine after a SD: Fe (fraction of oral dose excreted in urine)
timeFrame: Day 1 through end of study (Day 10)
measure: PK of TD-0714 in urine after a SD: Clr (renal clearance)
timeFrame: Day 1 through end of study (Day 10)
Other outcomes:
measure: Pharmacodynamics assessments for plasma atrial natriuretic peptide (ANP) concentrations
timeFrame: The day before dosing (Day -1) to the day after dosing (Day 2)
measure: Pharmacodynamics assessments for urine atrial natriuretic peptide (ANP) concentrations
timeFrame: The day before dosing (Day -1) to the day after dosing (Day 2)
measure: Pharmacodynamics assessments for plasma cyclic guanosine monophosphate (cGMP) concentrations
timeFrame: The day before dosing (Day -1) to the day after dosing (Day 2)
measure: Pharmacodynamics assessments for urine cyclic guanosine monophosphate (cGMP) concentrations
timeFrame: The day before dosing (Day -1) to the day after dosing (Day 2)
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References: