Cachexia
Conditions
Keywords
FTIH, pharmacokinetics, SARM, safety
Brief summary
This study is the first administration of GSK2881078 to humans. The intention of this study is to provide sufficient confidence in the safety of the molecule to inform progression to further repeat dose and proof of concept studies. This study will include approximately 52 subjects and consist of 2 parts. Part A will consist of two cohorts of 8 subjects to assess the safety, tolerability, and pharmacokinetic (PK) of ascending single oral doses of GSK2881078. Cohorts 1 and 2 will include healthy male subjects. Part B (Cohorts 3, 4 and 5) will include three cohorts of 12 healthy male subjects to examine the safety, tolerability, PK, and pharmacodynamic (PD) of repeated doses of GSK2881078 over 14 days. The total duration of the study including screening and follow-up, is not expected to exceed 70 days.
Interventions
DRUGGSK2881078
Hot melt solution within Capsule for oral single ascending doses or repeat dose administration with planned dose level and strength of 0.1, 0.3, 1.0, 2.0, 4.0, 8.0, and 10.0 mg
DRUGPlacebo
Hot melt solution within Capsule for oral single ascending doses or repeat doses administration.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Males between 18 and 50 years of age (inclusive), at the time of signing the informed consent form * Body weight \>= 50 kilogram (kg) and Body Mass Index (BMI) within the range 19 - 32 kg/meter square (m\^2) (inclusive), where BMI= weight in kg/ height in m\^2 * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the Lifestyle Section of the protocol. This criterion must be followed through the completion of the follow-up visit. * Average QTcF \<450millisecond (msec); or QTcF \<480msec in subjects with Bundle Branch Block. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria
* Subjects with a history of clinically significant endocrine, gastrointestinal, hepatic, cardiovascular, neurological, haematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases. * Subjects with a history at any time in the past of coronary artery disease, congestive heart failure, angina, myocardial infarction, any cardiac surgery, valvular heart disease, clinically significant arrhythmia, dyspnea, pulmonary edema, stroke, or transient ischemic attack. ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events following repeat doses as a measure of safety and tolerability | 28 days | AEs will be collected from the start of Study Treatment and until the follow-up contact |
| Laboratory parameters following repeat doses as measure of safety and tolerability | Up to 56 days | Laboratory parameters include: hematology, clinical chemistry, and urinalysis |
| Number of participants with adverse events following single doses as a measure of safety and tolerability | 33 days | AEs will be collected from the start of Study Treatment and until the follow-up contact |
| Vital sign assessment following single doses as a measure of safety and tolerability | Up to 61 days | Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate |
| Vital sign assessment following repeat doses as a measure of safety and tolerability | Up to 56 days | Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate |
| Cardiac telemetry following single doses as a measure of safety and tolerability | Up to 19 days | Continuous cardiac telemetry will be performed for at least 12 hours post dose in each treatment period in Part A. |
| Cardiac telemetry following repeat doses as a measure of safety and tolerability | 14 days | Continuous cardiac telemetry will be performed for at least 8 hours post dose in Days 1, 4, 7, 10, and 14 in Part B |
| Electrocardiogram (ECG) assessment following single doses as a measure of safety and tolerability | Up to 61 days | 12-lead ECGs will be obtained during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF intervals) at each timepoint |
| ECG assessment following repeat doses as a measure of safety and tolerability | Up to 56 days | 12-lead ECGs will be obtained during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF intervals) at each timepoint |
| Laboratory parameters assessment following single doses as a measure of safety and tolerability | Up to 61 days | Laboratory parameters include: hematology, clinical chemistry, and urinalysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of PK parameters following repeat doses | Up to 17 days | PK parameters include: AUC (0-infinite), area under the concentration-time curve over the dosing interval (AUC \[0-tau\]), AUC (0-t), Cmax, tmax, t1/2 and accumulation ratio |
| Composite of PK parameters following single doses | PK samples will be collected at pre-dose and 0.2, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose in each of the four dosing session | PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0-infinite\]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC\[0-t\]), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2) |
Countries
United States
Outcome results
None listed