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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of GSK2881078 in Single and Repeat Doses

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ClinicalTrials.gov Identifier: NCT02045940
Recruitment Status : Completed
First Posted : January 27, 2014
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 23, 2014
First Posted Date  ICMJE January 27, 2014
Last Update Posted Date July 24, 2018
Actual Study Start Date  ICMJE January 20, 2014
Actual Primary Completion Date March 26, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2014)
  • 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
  • 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
  • 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 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02045940 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2014)
  • Composite of PK parameters following single doses [ Time Frame: 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)
  • Composite of PK parameters following repeat doses [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of GSK2881078 in Single and Repeat Doses
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cachexia
Intervention  ICMJE
  • Drug: GSK2881078
    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
  • Drug: Placebo
    Hot melt solution within Capsule for oral single ascending doses or repeat doses administration.
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: GSK2881078
    • Drug: Placebo
  • Experimental: 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
    Interventions:
    • Drug: GSK2881078
    • Drug: Placebo
  • Experimental: 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
    Interventions:
    • Drug: GSK2881078
    • Drug: Placebo
  • Experimental: 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
    Interventions:
    • Drug: GSK2881078
    • Drug: Placebo
  • Experimental: 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
    Interventions:
    • Drug: GSK2881078
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 6, 2015)
99
Original Estimated Enrollment  ICMJE
 (submitted: January 23, 2014)
52
Actual Study Completion Date  ICMJE March 26, 2015
Actual Primary Completion Date March 26, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Subjects with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study:

Liver function tests - Alanine aminotransferase, Direct Bilirubin, or Albumin more than 10% outside the normal reference range (<0.9 x lower limit of normal [LLN] or >1.1 x upper limit of normal [ULN]) Renal function - Creatinine >1.6milligrams (mg)/deciliter (dL) with an age appropriate glomerular filtration rate<=60 (mL/minute/1.73 m^2).

Electrolytes - Sodium more than ± 5milliequivalents/Liter outside the normal reference range, Potassium or Calcium more than 10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN) Metabolic - Glucose more than 10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN) and Total Cholesterol > 240mg/dL Muscle - creatine phosphokinase >2.0 x ULN Hematology - Hemoglobin, white blood cells, Neutrophils, or Platelets more than 10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN) Prostate Specific Antigen >2.5nanogram/mL

  • A positive test for human immuno virus antibody
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day
  • Unable to refrain from prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication and throughout the study, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months (12 weeks), 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Where participation in the study would result in donation of blood or blood products in excess of 500mL within a 56-day period.
  • Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02045940
Other Study ID Numbers  ICMJE 200181
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP