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

NCT02045940 | Completed Phase 1

• 1 other identifier: 200181
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 2

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.

Conditions

Cachexia

Keywords

FTIH; pharmacokinetics; SARM; safety

Outcome Measures

Primary Outcomes (10)

• Vital sign assessment following single doses as a measure of safety and tolerability

  Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate

  Up to 61 days

• Vital sign assessment following repeat doses as a measure of safety and tolerability

  Vital signs include: systolic blood pressure, diastolic blood pressure and heart rate

  Up to 56 days

• Cardiac telemetry following single doses as a measure of safety and tolerability

  Continuous cardiac telemetry will be performed for at least 12 hours post dose in each treatment period in Part A.

  Up to 19 days

• Cardiac telemetry following repeat doses as a measure of safety and tolerability

  Continuous cardiac telemetry will be performed for at least 8 hours post dose in Days 1, 4, 7, 10, and 14 in Part B

  14 days

• Electrocardiogram (ECG) assessment following single doses as a measure of safety and tolerability

  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

  Up to 61 days

• ECG assessment following repeat doses as a measure of safety and tolerability

  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

  Up to 56 days

• Laboratory parameters assessment following single doses as a measure of safety and tolerability

  Laboratory parameters include: hematology, clinical chemistry, and urinalysis

  Up to 61 days

• Laboratory parameters following repeat doses as measure of safety and tolerability

  Laboratory parameters include: hematology, clinical chemistry, and urinalysis

  Up to 56 days

• Number of participants with adverse events following single doses as a measure of safety and tolerability

  AEs will be collected from the start of Study Treatment and until the follow-up contact

  33 days

• Number of participants with adverse events following repeat doses as a measure of safety and tolerability

  AEs will be collected from the start of Study Treatment and until the follow-up contact

  28 days

Secondary Outcomes (2)

• 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

Study Arms (5)

Cohort 1

EXPERIMENTAL

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

Drug: GSK2881078; Drug: Placebo

Cohort 2

EXPERIMENTAL

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

Drug: GSK2881078; Drug: Placebo

Cohort 3

EXPERIMENTAL

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

Drug: GSK2881078; Drug: Placebo

Cohort 4

EXPERIMENTAL

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

Drug: GSK2881078; Drug: Placebo

Cohort 5

EXPERIMENTAL

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

Drug: GSK2881078; Drug: Placebo

Interventions

GSK2881078 DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo DRUG

Hot melt solution within Capsule for oral single ascending doses or repeat doses administration.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• Results for study 200181 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Cachexia

Interventions

GSK2881078

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: January 27, 2014
• Study Start: January 20, 2014
• Primary Completion: March 26, 2015
• Study Completion: March 26, 2015
• Last Updated: July 24, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (2)