A Randomized Double Blinded (Sponsor Unblind), Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM) in Single and Repeat Doses in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- GSK2881078
- Conditions
- Cachexia
- Sponsor
- GlaxoSmithKline
- Enrollment
- 99
- Locations
- 1
- Primary Endpoint
- Vital sign assessment following repeat doses as a measure of safety and tolerability
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
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 exclusion criteria: Heart rate-\<40 and \>100 beats per minute, PR Interval-\<120 and \>200msec, QRS duration-\<70 and \>110msec.
- •Subjects with a history of malignancy that is not in complete remission for at least 5 years or 1 year for non-melanoma skin carcinoma
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •History of drug or alcohol abuse within 5 years prior to the Screening Period.
- •History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 milliliter \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- •Subjects with a family history of early onset prostate cancer or multiple members with prostate cancer.
- •A positive pre-study drug or alcohol screen.
- •Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Arms & Interventions
Cohort 1
Participants will receive one of the following four treatment sequences in four study period (one treatment per period). Sequence 1=Placebo, dose level (DL) 2, DL3, and DL4. Sequence 2=DL1, placebo, DL2, and DL4. Sequence 3=DL1, DL2, placebo, and DL4. Sequence 4=DL1, DL2, DL3, and placebo
Intervention: GSK2881078
Cohort 1
Participants will receive one of the following four treatment sequences in four study period (one treatment per period). Sequence 1=Placebo, dose level (DL) 2, DL3, and DL4. Sequence 2=DL1, placebo, DL2, and DL4. Sequence 3=DL1, DL2, placebo, and DL4. Sequence 4=DL1, DL2, DL3, and placebo
Intervention: Placebo
Cohort 3
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A
Intervention: Placebo
Cohort 2
Participants will receive one of the following four treatment sequences in four study period (one treatment per period). Sequence 5=Placebo, DL5, DL6, and DL7. Sequence 6=DL4, placebo, DL6, and DL7. Sequence 7=DL4, DL5, placebo, and DL7. Sequence 8=DL4, DL5, DL6, and placebo
Intervention: GSK2881078
Cohort 2
Participants will receive one of the following four treatment sequences in four study period (one treatment per period). Sequence 5=Placebo, DL5, DL6, and DL7. Sequence 6=DL4, placebo, DL6, and DL7. Sequence 7=DL4, DL5, placebo, and DL7. Sequence 8=DL4, DL5, DL6, and placebo
Intervention: Placebo
Cohort 3
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A
Intervention: GSK2881078
Cohort 4
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A and preceding repeat dose Cohort
Intervention: GSK2881078
Cohort 4
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A and preceding repeat dose Cohort
Intervention: Placebo
Cohort 5
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A and preceding repeat dose Cohorts
Intervention: GSK2881078
Cohort 5
Participants will receive repeat doses of GSK2881078 or placebo in a 3:1 randomization ratio for 14 days. The dose level will depend upon results from Part A and preceding repeat dose Cohorts
Intervention: Placebo
Outcomes
Primary Outcomes
Vital sign assessment following repeat doses as a measure of safety and tolerability
Time Frame: Up to 56 days
Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
Number of participants with adverse events following single doses as a measure of safety and tolerability
Time Frame: 33 days
AEs will be collected from the start of Study Treatment and until the follow-up contact
Cardiac telemetry following single doses as a measure of safety and tolerability
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: Up to 61 days
Laboratory parameters include: hematology, clinical chemistry, and urinalysis
Laboratory parameters following repeat doses as measure of safety and tolerability
Time Frame: Up to 56 days
Laboratory parameters include: hematology, clinical chemistry, and urinalysis
Number of participants with adverse events following repeat doses as a measure of safety and tolerability
Time Frame: 28 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
Time Frame: Up to 61 days
Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate
Secondary Outcomes
- 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)
- Composite of PK parameters following repeat doses(Up to 17 days)