CachexiaPhase 1NCT01696604
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2849466 in Healthy Male Subjects
A Phase 1 study testing GSK2849466 in people with Cachexia, run by GlaxoSmithKline at 1 site in United States.
Trial summary
This study is the first administration of GSK2849466 in humans. This will be a single centre, randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat oral doses up to 14 days to healthy male… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cachexia
- What is being tested?
- GSK2849466
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2012to 3 May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 (m)^2 (inclusive), where BMI = (weight in kg)/(height in meters)^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 GlaxoSmithKline (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.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Average corrected QT interval using Fridericia's formulas (QTcF) <450 milliseconds (msec); or QTcF <480 msec in subjects with Bundle Branch Block.
Who cannot join
- Subjects with a history of clinically significant endocrine, gastrointestinal, hepatic, cardiovascular, neurological, hematological, 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 >200 msec; QRS duration <70 and >110 msec.
- 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.
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- 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 grams (g) of alcohol: 12 ounces (360 millilitre [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.
- 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 transaminase (ALT), Direct Bilirubin, or Albumin >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 <1.6 mg/ deciliter (dl) with an age appropriate Glomerular filtration rate (GFR) >=60 mL/min/1.73 m^2), Electrolytes - Sodium > +,- 5 milliequivalents of solute per litre of solvent (mEq/L) outside the normal reference range, Potassium or Calcium >10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN), Metabolic - Glucose >10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN) and Total Cholesterol >240 mg/dl, Muscle - creatine phosphokinase >2.0 x ULN, Hematology - Hemoglobin, WBC, Neutrophils, or Platelets >10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN), Prostate Specific Antigen (PSA) >=2.5 nanogram (ng)/mL.
- A positive test for human immunodeficiency virus (HIV) 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 500 mL within a 56-day period.
- Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
- Unwillingness or inability to follow the procedures outlined in the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Randomized, Blinded, Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM), GSK2849466, in Single and Repeat Doses, With and Without Food, in Healthy Male Subjects
This study is the first administration of GSK2849466 in humans. This will be a single centre, randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat oral doses up to 14 days to healthy male subjects. Part A will be a randomized placebo controlled and 4-way crossover study. It will include two cohorts of 8 subjects each. In each cohort there will be 4 study periods each approximately of 1 week including 6 days of washout. Each subject will receive a total of 3 active doses as ascending single oral dose of GSK2849466 and 1 placebo dose during the course of their participation in the study. The first ("bridging dose") dose provided to subjects in Cohort 2 will be the same as the last dose provided to subjects in Cohort 1. The single doses of GSK2849466 planned in Part A of this study are: 0.01, 0.03, 0.1, and 0.3 milligram (mg) in Cohort 1 and 0.3, 1, 3, and 10 mg in Cohort 2. In cohorts 1 and 2 all available safety, tolerability, and PK data will be reviewed prior to each dose escalation. The dosing schedule in Part A may be adjusted to expand a cohort or to add an additional cohort(s) in order to further evaluate additional doses or repeat evaluation of a dose level already studied. Part B will be a randomized placebo controlled, parallel group study. It will include three cohorts of 12 subjects each. Each subject will receive repeat doses of GSK2849466 over 14 days. The doses chosen for Part B will be based on the safety, tolerability, and PK data from Part A. Subjects in Cohort 4 (and/or an another cohort [s] as determined based on Part A PK data) will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7 when subjects will receive a standard meal 30 minutes prior to dosing. Part B will provide sufficient safety and tolerability data to bridge to longer duration studies. The study duration, including screening and follow-up, is not expected to exceed 70 days for subjects in the study.
- Conditions
- Cachexia
- Being tested
- GSK2849466, Placebo
- Keywords
- safety, pharmacokinetics, FTIH, SARM
- Medical subject headings
- Cachexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2849466Drug
GSK2849466 will be available as capsules of dose strengths 0.01, 0.1, 1.0, and 2.5 mg.
PlaceboDrug
Matching placebo capsules will be available.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort 1-GSK2849466 | Experimental | The subjects will receive single planned dose of GSK284946 in ascending order (0.01, 0.03, 0.1, and 0.3 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period. Receives: Drug: GSK2849466 |
| Part A: Cohort 1-Placebo | Experimental | The subjects will receive single dose of matching placebo in one of the 4 treatment periods. Receives: Drug: Placebo |
| Part A: Cohort 2-GSK2849466 | Experimental | The subjects will receive single planned dose of GSK284946 in ascending order (0.3, 1, 3, and 10 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period in one of the 4 treatment periods. Receives: Drug: GSK2849466 |
| Part A: Cohort 2-Placebo | Experimental | The subjects will receive single dose of matching placebo in one of the 4 treatment periods. Receives: Drug: Placebo |
| Part B: Cohort 3-GSK2849466 (Repeat dose 1) | Experimental | The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. Receives: Drug: GSK2849466 |
| Part B: Cohort 3-Placebo (Repeat dose 1) | Experimental | The subjects will receive repeat dose of matching placebo. Receives: Drug: Placebo |
| Part B: Cohort 4-GSK2849466 (Repeat dose 2) | Experimental | The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. In Cohort 4 subjects will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7. Receives: Drug: GSK2849466 |
| Part B: Cohort 4-Placebo (Repeat dose 2) | Experimental | The subjects will receive repeat doses of matching placebo. Receives: Drug: Placebo |
| Part B: Cohort 5-GSK2849466 (Repeat dose 3) | Experimental | The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo Receives: Drug: GSK2849466 |
| Part B: Cohort 5-Placebo (Repeat dose 3) | Experimental | The subjects will receive repeat doses of matching placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s
Safety and tolerability parameters will include recording of AEs, throughout the study.
Measured: 28 days
Safety and tolerability of repeat doses of GSK2849466 as assessed by number of subjects with AEs
Safety and tolerability parameters will include recording of AEs, throughout the study.
Measured: 14 days
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in electrocardiogram (ECG) readings
Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
Measured: 28 days
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in ECG readings
Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
Measured: 14 days
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
Measured: 28 days
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
Measured: 14 days
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in heart rate
Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
Measured: 28 days
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in heart rate
Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
Measured: 14 days
Safety and tolerability of GSK2849466 as assessed by change from Baseline in cardiac telemetry
Safety and tolerability parameters will include cardiac telemetry recording at Baseline and at end of the study.
Measured: Part A-Day 1 continuous at least 12 hours post-dose of each dosing session; Part B-Day 1, 4, 7, 10 and 14 continuous at least 8 hours post-dose
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
Measured: 28 days
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
Measured: 14 days
Secondary outcomes (9)
Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) following single doses of GSK2849466
The AUC(0-t) and AUC(0-inf) for GSK2849466 will be assessed following single doses of GSK2849466.
Measured: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Maximum concentration (Cmax) following single doses of GSK2849466
The Cmax of GSK2849466 will be assessed following single doses of GSK2849466.
Measured: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Time to maximum observed plasma drug concentration (Tmax) following single doses of GSK2849466
The Tmax for GSK2849466 will be assessed following single doses of GSK2849466.
Measured: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Terminal half-life (t1/2) following single doses of GSK2849466
The t1/2 for GSK2849466 will be assessed following single doses of GSK2849466.
Measured: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
The AUC(0-t), AUC(0-inf)) and AUC from time zero to the end of the dosing interval at steady state AUC(0-tau) following repeat doses of GSK2849466
The AUC(0-t), AUC(0-inf) and AUC(0-tau) following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
Measured: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The Cmax following repeat doses of GSK2849466
The Cmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
Measured: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The Tmax following repeat doses of GSK2849466
The Tmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
Measured: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The t1/2 following repeat doses of GSK2849466
The t1/2 following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
Measured: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The estimation of an accumulation ratio following repeat doses of GSK2849466
The estimation of an accumulation ratio following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
Measured: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2012 (estimated)
- Study start26 Sep 2012
- Primary completion3 May 2013
- Study completion3 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CachexiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01696604
- Sponsor's protocol ID
- 116715
- Status last verified
- Jun 2017
- First submitted
- 27 Sep 2012
- Last updated
- 7 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Randomized, Blinded, Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM), GSK2849466, in Single and Repeat Doses, With and Without Food, in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT01696604
- Acronym / sponsor ID
- 116715
- Conditions
- Cachexia
- Keywords
- safety, pharmacokinetics, FTIH, SARM
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2012 (actual)
- Primary completion
- 3 May 2013 (actual)
- Study completion
- 3 May 2013 (actual)
- First posted
- 1 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is the first administration of GSK2849466 in humans. This will be a single centre, randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat oral doses up to 14 days to healthy male subjects. Part A will be a randomized placebo controlled and 4-way crossover study. It will include two cohorts of 8 subjects each. In each cohort there will be 4 study periods each approximately of 1 week including 6 days of washout. Each subject will receive a total of 3 active doses as ascending single oral dose of GSK2849466 and 1 placebo dose during the course of their participation in the study. The first ("bridging dose") dose provided to subjects in Cohort 2 will be the same as the last dose provided to subjects in Cohort 1. The single doses of GSK2849466 planned in Part A of this study are: 0.01, 0.03, 0.1, and 0.3 milligram (mg) in Cohort 1 and 0.3, 1, 3, and 10 mg in Cohort 2. In cohorts 1 and 2 all available safety, tolerability, and PK data will be reviewed prior to each dose escalation. The dosing schedule in Part A may be adjusted to expand a cohort or to add an additional cohort(s) in order to further evaluate additional doses or repeat evaluation of a dose level already studied. Part B will be a randomized placebo controlled, parallel group study. It will include three cohorts of 12 subjects each. Each subject will receive repeat doses of GSK2849466 over 14 days. The doses chosen for Part B will be based on the safety, tolerability, and PK data from Part A. Subjects in Cohort 4 (and/or an another cohort [s] as determined based on Part A PK data) will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7 when subjects will receive a standard meal 30 minutes prior to dosing. Part B will provide sufficient safety and tolerability data to bridge to longer duration studies. The study duration, including screening and follow-up, is not expected to exceed 70 days for subjects in the study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Part A: Cohort 1-GSK2849466 | Experimental | Drug: GSK2849466The subjects will receive single planned dose of GSK284946 in ascending order (0.01, 0.03, 0.1, and 0.3 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period. |
| Part A: Cohort 1-Placebo | Experimental | Drug: PlaceboThe subjects will receive single dose of matching placebo in one of the 4 treatment periods. |
| Part A: Cohort 2-GSK2849466 | Experimental | Drug: GSK2849466The subjects will receive single planned dose of GSK284946 in ascending order (0.3, 1, 3, and 10 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period in one of the 4 treatment periods. |
| Part A: Cohort 2-Placebo | Experimental | Drug: PlaceboThe subjects will receive single dose of matching placebo in one of the 4 treatment periods. |
| Part B: Cohort 3-GSK2849466 (Repeat dose 1) | Experimental | Drug: GSK2849466The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. |
| Part B: Cohort 3-Placebo (Repeat dose 1) | Experimental | Drug: PlaceboThe subjects will receive repeat dose of matching placebo. |
| Part B: Cohort 4-GSK2849466 (Repeat dose 2) | Experimental | Drug: GSK2849466The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. In Cohort 4 subjects will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7. |
| Part B: Cohort 4-Placebo (Repeat dose 2) | Experimental | Drug: PlaceboThe subjects will receive repeat doses of matching placebo. |
| Part B: Cohort 5-GSK2849466 (Repeat dose 3) | Experimental | Drug: GSK2849466The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo |
| Part B: Cohort 5-Placebo (Repeat dose 3) | Experimental | Drug: PlaceboThe subjects will receive repeat doses of matching placebo. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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 (m)^2 (inclusive), where BMI = (weight in kg)/(height in meters)^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 GlaxoSmithKline (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.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Key exclusion criteria (20 listed)
- Subjects with a history of clinically significant endocrine, gastrointestinal, hepatic, cardiovascular, neurological, hematological, 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 >200 msec; QRS duration <70 and >110 msec.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2849466GSK2849466 will be available as capsules of dose strengths 0.01, 0.1, 1.0, and 2.5 mg. | Drug | Part A: Cohort 1-GSK2849466, Part A: Cohort 2-GSK2849466, Part B: Cohort 3-GSK2849466 (Repeat dose 1), Part B: Cohort 4-GSK2849466 (Repeat dose 2), Part B: Cohort 5-GSK2849466 (Repeat dose 3) |
| PlaceboMatching placebo capsules will be available. | Drug | Part A: Cohort 1-Placebo, Part A: Cohort 2-Placebo, Part B: Cohort 3-Placebo (Repeat dose 1), Part B: Cohort 4-Placebo (Repeat dose 2), Part B: Cohort 5-Placebo (Repeat dose 3) |
Primary outcome
Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s
Time frame: 28 days
Safety and tolerability parameters will include recording of AEs, throughout the study.
Safety and tolerability of repeat doses of GSK2849466 as assessed by number of subjects with AEs
Time frame: 14 days
Safety and tolerability parameters will include recording of AEs, throughout the study.
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in electrocardiogram (ECG) readings
Time frame: 28 days
Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in ECG readings
Time frame: 14 days
Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
Time frame: 28 days
Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
Time frame: 14 days
Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in heart rate
Time frame: 28 days
Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in heart rate
Time frame: 14 days
Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
Safety and tolerability of GSK2849466 as assessed by change from Baseline in cardiac telemetry
Time frame: Part A-Day 1 continuous at least 12 hours post-dose of each dosing session; Part B-Day 1, 4, 7, 10 and 14 continuous at least 8 hours post-dose
Safety and tolerability parameters will include cardiac telemetry recording at Baseline and at end of the study.
Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
Time frame: 28 days
Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
Time frame: 14 days
Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
9 secondary outcomes
Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) following single doses of GSK2849466
Time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Maximum concentration (Cmax) following single doses of GSK2849466
Time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Time to maximum observed plasma drug concentration (Tmax) following single doses of GSK2849466
Time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
Terminal half-life (t1/2) following single doses of GSK2849466
Time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
The AUC(0-t), AUC(0-inf)) and AUC from time zero to the end of the dosing interval at steady state AUC(0-tau) following repeat doses of GSK2849466
Time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The Cmax following repeat doses of GSK2849466
Time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The Tmax following repeat doses of GSK2849466
Time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The t1/2 following repeat doses of GSK2849466
Time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
The estimation of an accumulation ratio following repeat doses of GSK2849466
Time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 116715 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2849466 in people with Cachexia, run by GlaxoSmithKline at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s (time frame: 28 days). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.