Healthy
Conditions
Keywords
Single ascending dose, volunteers, Phase 1, first-in-human, TD-0714
Brief summary
Single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-0714 in healthy subjects.
Interventions
DRUGTD-0714
One time dosing in capsule formulation
DRUGPlacebo Comparator
One time dosing in capsule formulation
Sponsors
Theravance Biopharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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: 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) |
| PK of TD-0714 in plasma after a SD: time to last measurable concentration (Tlast) | Day 1 through end of study (Day 10) |
| 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: 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 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) |
Other
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
Countries
United States
Outcome results
None listed