Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03627494
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : October 8, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The FTIH study with GSK3439171A will evaluate the safety of GSK3439171A in healthy subjects in order to avoid confounding factors due to the disease or concomitant drugs in patients. The study design is based on pre-clinical findings for GSK3439171A, contributing to the frequency, type and duration of safety assessment and monitoring during treatment periods in each cohort. The single dose assessments in Part A will be conducted to determine safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the study intervention in individuals before progressing to doses explored further in other parts of the study and will allow for any adjustments needed based on emerging safety, tolerability, and PK information. Part A will also serve to identify a dose for use in examining the effect of food on GSK3439171A exposure in Part C. In Part B, a single dose safety, tolerability and PK will be collected followed by progression of these subjects to the repeat dose portion of the study. The up to 14-day dosing was chosen as it is thought to provide sufficient safety and tolerability data to bridge to longer duration studies. The dosing period can be adjusted depending on PK and PD data collected in Part A of the study. Part B will involve more detailed PK/PD/metabolite assessments to better understand the impact of GSK3439171A on target engagement and metabolism in humans. Approximately 150 subjects will be screened to achieve 75 randomly assigned to study intervention. Duration for Part A, B and C will be approximately 10 weeks, 9 weeks and 8 weeks respectively.

Condition or disease Intervention/treatment Phase
Muscular Dystrophies Drug: GSK3439171A Drug: Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Part A is a Crossover group single ascending dose study with 2 arms per cohort that is subject and investigator blinded. Part B is a Parallel group repeat dose study with 2 arms per cohort that is subject and investigator blinded. Part C is a Crossover group food effect study with 2 arms per cohort that is not-masked."
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Three-Part FTIH Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Oral Doses of GSK3439171A, in a Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Dose Escalation Study and to Evaluate the Effect of Food on a Single Oral Dose of GSK3439171A in Healthy Adult Participants
Actual Study Start Date : August 30, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A: P1,PBO/GSK3439171A Dose 2/GSK3439171A Dose 3
Subjects will administer oral solution with doses 0.5 milligram (mg) up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence placebo (PBO) followed by Dose 2 of GSK3439171A followed by Dose 3 of GSK3439171A in period 1 (P1). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P1, GSK3439171A Dose 1/ PBO/GSK3439171A Dose 3
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and PBO as per randomized sequence: Dose 1 of GSK3439171A followed by PBO followed by Dose 3 of GSK3439171A in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P1, GSK3439171A Dose 1/ GSK3439171A Dose 2/ PBO
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 1 of GSK3439171A followed by Dose 2 of GSK3439171A followed by PBO in P1. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P2, PBO/GSK3439171A Dose 5/GSK3439171A Dose 6
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 5 of GSK3439171A followed by Dose 6 of GSK3439171A in period 2 (P2). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P2, GSK3439171A Dose 4/ PBO/GSK3439171A Dose 6
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by PBO followed by Dose 6 of GSK3439171A in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P2, GSK3439171A Dose 4/ GSK3439171A Dose 5/ PBO
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 4 of GSK3439171A followed by Dose 5 of GSK3439171A followed by PBO in P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P3, PBO/GSK3439171A Dose 8/GSK3439171A Dose 9
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: PBO followed by Dose 8 of GSK3439171A followed by Dose 9 of GSK3439171A in Period 3 (P3). There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P3, GSK3439171A Dose 7/ PBO/GSK3439171A Dose 9
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by PBO followed by Dose 9 of GSK3439171A in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part A: P3, GSK3439171A Dose 7/ GSK3439171A Dose 8/ PBO
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A and placebo as per randomized sequence: Dose 7 of GSK3439171A followed by Dose 8 of GSK3439171A followed by PBO in P3. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part B: GSK3439171A
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of GSK3439171A in part B
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Placebo Comparator: Part B: Placebo
Subjects will administer oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards of Placebo in part B
Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part C: GSK3439171A fed followed by GSK3439171A fasted
Subjects will administer GSK3439171A in Fed condition in Part C P1 followed by GSK3439171A in fasted condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Experimental: Part C: GSK3439171A fasted followed by GSK3439171A fed
Subjects will administer GSK3439171A in fasted condition in Part C P1 followed by GSK3439171A in fed condition in Part C P2. There will be a washout period of 7 days or 5 half-lives, whichever is longer in between the doses.
Drug: GSK3439171A
Oral solution with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards

Drug: Placebo
Placebo oral solution to match with doses 0.5 mg up to 4.5 mg and capsule for doses 5 mg and upwards




Primary Outcome Measures :
  1. Part A: Number of subjects with Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to 6 weeks ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose that results in death and is life-threatening. Number of subjects with AE and SAE for Part A will be reported.

  2. Part B: Number of subjects with AE and SAE [ Time Frame: Up to 5 weeks ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose that results in death and is life-threatening. Number of subjects with AE and SAE for Part B will be reported.

  3. Part C: Number of subjects with AE and SAE [ Time Frame: Up to 4 weeks ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose that results in death and is life-threatening. Number of subjects with AE and SAE for Part C will be reported.

  4. Part A: Number of subjects with abnormal Hematology Values [ Time Frame: Up to 6 weeks ]
    Number of subjects with abnormal Hematology values including: Platelet Count, red blood cells, white blood cells, Reticulocyte, Hemoglobin, Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, mean corpuscular volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Prothrombin time and Prothrombin time for Part A will be reported.

  5. Part B: Number of subjects with abnormal Hematology Values [ Time Frame: Up to 5 weeks ]
    Number of subjects with abnormal Hematology values including: Platelet Count, red blood cells, white blood cells, Reticulocyte, Hemoglobin, Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, mean corpuscular volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Prothrombin time and Prothrombin time for Part B will be reported.

  6. Part C: Number of subjects with abnormal Hematology Values [ Time Frame: Up to 4 weeks ]
    Number of subjects with abnormal Hematology values including: Platelet Count, red blood cells, white blood cells, Reticulocyte, Hemoglobin, Hematocrit, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, mean corpuscular volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Prothrombin time and Prothrombin time for Part C will be reported.

  7. Part A: Number of subjects with abnormal Clinical Chemistry Values [ Time Frame: Up to 6 weeks ]
    Number of subjects with abnormal Clinical Chemistry values including: Blood Urea Nitrogen, Creatinine, Glucose, Sodium, Potassium, Chloride, Calcium, total carbon dioxide, Alkaline phosphatase, Gamma-glutamyl Transferase (GGT), Alanine Transferase (ALT), Aspartate Aminotransferase (AST), Total and direct bilirubin, Uric Acid, Albumin, Total Protein, Creatine Phosphokinase for Part A will be reported.

  8. Part B: Number of subjects with abnormal Clinical Chemistry Values [ Time Frame: Up to 5 weeks ]
    Number of subjects with abnormal Clinical Chemistry values including: Blood Urea Nitrogen, Creatinine, Glucose, Sodium, Potassium, Chloride, Calcium, total carbon dioxide, Alkaline phosphatase, GGT, ALT, AST, Total and direct bilirubin, Uric Acid, Albumin, Total Protein, Creatine Phosphokinase for Part B will be reported.

  9. Part C: Number of subjects with abnormal Clinical Chemistry Values [ Time Frame: Up to 4 weeks ]
    Number of subjects with abnormal Clinical Chemistry values including: Blood Urea Nitrogen, Creatinine, Glucose, Sodium, Potassium, Chloride, Calcium, total carbon dioxide, Alkaline phosphatase, GGT, ALT, AST, Total and direct bilirubin, Uric Acid, Albumin, Total Protein, Creatine Phosphokinase for Part C will be reported.

  10. Part A: Number of subjects with abnormal Urinalysis Values [ Time Frame: Up to 6 weeks ]
    Number of subjects with abnormal Urinalysis values including: Specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and Microscopic examination for part A will be reported.

  11. Part B: Number of subjects with abnormal Urinalysis Values [ Time Frame: Up to 5 weeks ]
    Number of subjects with abnormal Urinalysis values including: Specific gravity, pH, glucose, protein, blood and ketones by dipstick and Microscopic examination for part B will be reported.

  12. Part C: Number of subjects with abnormal Urinalysis Values [ Time Frame: Up to 4 weeks ]
    Number of subjects with abnormal Urinalysis values including: Specific gravity, pH, glucose, protein, blood and ketones by dipstick and Microscopic examination for part C will be reported.

  13. Part B: Number of subjects with abnormal Hormone Assessment [ Time Frame: Days -1 and 16 ]
    Number of subjects with abnormal Hormone Assessments including Luteinizing hormone (LH), Follicle stimulating hormone (FSH), Total Testosterone, Dihydrotestosterone (DHT), Adrenocorticotropic hormone (ACTH), Thyroid stimulating hormone (TSH), cortisol, Triiodothyronine (T3) and Free Thyroxine (T4) will be reported.

  14. Part A: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure. [ Time Frame: Up to 6 weeks ]
    Blood pressure will be assessed with a completely automated device. Blood pressure measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions Number of subjects with abnormal Systolic and diastolic blood pressure for Part A will be reported.

  15. Part B: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure. [ Time Frame: Up to 5 weeks ]
    Blood pressure will be assessed with a completely automated device. Blood pressure measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions Number of subjects with abnormal Systolic and diastolic blood pressure for Part B will be reported.

  16. Part C: Number of subjects with abnormal Vital Signs: Systolic and diastolic blood pressure. [ Time Frame: Up to 4 weeks ]
    Blood pressure will be assessed with a completely automated device. Blood pressure measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions Number of subjects with abnormal Systolic and diastolic blood pressure for Part C will be reported.

  17. Part A: Number of subjects with abnormal Vital Signs: Pulse rate [ Time Frame: Up to 6 weeks ]
    Pulse rate will be assessed with a completely automated device. Pulse measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions. Number of subjects with abnormal pulse rate for Part A will be reported.

  18. Part B: Number of subjects with abnormal Vital Signs: Pulse rate [ Time Frame: Up to 5 weeks ]
    Pulse rate will be assessed with a completely automated device. Pulse measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions. Number of subjects with abnormal pulse rate for Part B will be reported.

  19. Part C: Number of subjects with abnormal Vital Signs: Pulse rate [ Time Frame: Up to 4 weeks ]
    Pulse rate will be assessed with a completely automated device. Pulse measurements should be preceded by at least 5 minutes of rest in a supine position for the subject in a quiet setting without distractions. Number of subjects with abnormal pulse rate for Part C will be reported.

  20. Part A: Number of subjects with abnormal Vital Signs: Respiratory Rate [ Time Frame: Up to 6 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal respiratory rate for Part A will be reported.

  21. Part B: Number of subjects with abnormal Vital Signs: Respiratory Rate [ Time Frame: Up to 5 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal respiratory rate for Part B will be reported.

  22. Part C: Number of subjects with abnormal Vital Signs: Respiratory Rate [ Time Frame: Up to 4 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal respiratory rate for Part C will be reported.

  23. Part A: Number of subjects with abnormal Vital Signs: Oral temperature [ Time Frame: Up to 6 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal Oral temperature for Part A will be reported.

  24. Part B: Number of subjects with abnormal Vital Signs: Oral temperature [ Time Frame: Up to 5 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal Oral temperature for Part B will be reported.

  25. Part C: Number of subjects with abnormal Vital Signs: Oral temperature [ Time Frame: Up to 4 weeks ]
    Vital signs will be measured in a supine position after 5 minutes rest. Number of subjects with abnormal Oral temperature for Part C will be reported.

  26. Part A: Number of subjects with abnormal Electrocardiogram (ECG) findings [ Time Frame: Up to 6 weeks ]
    Triplicate 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT Interval (QT), and QT interval corrected (QTc). ECGs will be recorded whilst the subject is in a supine position, having rested in this position for at least 15 minutes. Number of subjects with abnormal ECG findings for Part A will be reported.

  27. Part B: Number of subjects with abnormal ECG findings [ Time Frame: Up to 5 weeks ]
    Triplicate 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. ECGs will be recorded whilst the subject is in a supine position, having rested in this position for at least 15 minutes. Number of subjects with abnormal ECG findings for Part B will be reported.

  28. Part C: Number of subjects with abnormal ECG findings [ Time Frame: Up to 4 weeks ]
    Triplicate 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. ECGs will be recorded whilst the subject is in a supine position, having rested in this position for at least 15 minutes. Number of subjects with abnormal ECG findings for Part C will be reported.

  29. Part A: Area under the plasma drug concentration versus time curve (AUC(0-T) of GSK3439171A following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected to evaluate PK parameters.

  30. Part B: AUC(0-T) of GSK3439171A following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected to evaluate PK parameters.

  31. Part A: Area under the plasma drug concentration versus time curve (AUC(0-Inf) of GSK3439171A following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected to evaluate PK parameters.

  32. Part B: AUC(0-Inf) of GSK3439171A following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected to evaluate PK parameters.

  33. Part A: Maximum observed plasma drug concentration (Cmax) of GSK3439171A following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected to evaluate PK parameters.

  34. Part B: Cmax of GSK3439171A following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected to evaluate PK parameters.

  35. Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK3439171A following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected to evaluate PK parameters.

  36. Part B: Tmax of GSK3439171A following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected to evaluate PK parameters.

  37. Part A: Apparent terminal half-life (t1/2) of GSK3439171A following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected to evaluate PK parameters.

  38. Part B: t1/2 of GSK3439171A following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected to evaluate PK parameters.


Secondary Outcome Measures :
  1. Part C: AUC(0-t) of GSK3439171A [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters and to assess food effect.

  2. Part C: AUC(0-inf) of GSK3439171A [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose ]
    Blood samples will be collected at indicated time points to evaluate PK parameters and to assess food effect.

  3. Part C: Cmax of GSK3439171A [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters and to assess food effect.

  4. Part C: Tmax of GSK3439171A [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters and to assess food effect.

  5. Part C: t1/2 of GSK3439171A in fed state [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters and to assess food effect.

  6. Part A: Dose proportionality of GSK3439171A using AUC (0-T) following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters to assess dose proportionality

  7. Part A: Dose proportionality of GSK3439171A using AUC (0-Inf) following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters to assess dose proportionality

  8. Part A: Dose proportionality of GSK3439171A using Cmax following Single dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose in each period ]
    Blood samples will be collected at indicated time points to evaluate PK parameters to assess dose proportionality

  9. Part B: Dose proportionality of GSK3439171A using AUC (0-tau) following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected at indicated time points to evaluate PK parameters to assess dose proportionality

  10. Part B: Dose proportionality of GSK3439171A using Cmax following repeat dose [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected at indicated time points to evaluate PK parameters to assess dose proportionality

  11. Part B: AUC (Ro) of GSK3439171A following repeat oral doses [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected at indicated time points to evaluate PK parameters

  12. Part B: Ratio of Cmax (RCmax) of GSK3439171A following repeat oral doses [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected at indicated time points to evaluate PK parameters

  13. Part B: Steady-state ratio (Rss) of GSK3439171A following repeat oral doses [ Time Frame: Pre-dose, 5 minute, 30 minute, 1 hour, 1.5 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, 12 hour, 18 hour, 24 hour, 36 hour, and 48 hour post-dose on Days 1 and 16 ]
    Blood samples will be collected at indicated time points to evaluate PK parameters

  14. Part B: Trough plasma concentrations at the end of the dosing interval (Ctau) of GSK3439171A [ Time Frame: Pre-dose on Days 15 and 16 ]
    Blood samples will be collected at indicated time points to evaluate trough plasma concentration to assess if steady state is achieved.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only males are eligible for this study
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Subjects with Body weight >=50.0 kilograms (Kg) (110 lbs.) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per square meter (inclusive).
  • Only male subjects are eligible for this study. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male subjects are eligible to participate if they agree to the following during the their entire enrolment in the study plus an additional 5 days or 5 terminal half-lives (whichever is longer): Refrain from donating sperm plus either be abstinent from sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier (female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year)
  • Subjects must be capable of giving signed informed consent

Exclusion Criteria:

  • Subjects are excluded from the study if they have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Subjects are excluded from the study if they have any clinically significant abnormal vital signs
  • Subjects are excluded from the study if they have Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years
  • Subjects are excluded from the study if they have ALT >1.5 times upper limit of normal (ULN)
  • Subjects are excluded from the study if Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • Subjects are excluded from the study if they have current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subjects are excluded from the study if they have QTc >450 milliseconds
  • Subjects who are unable to refrain from the use of prescription or non-prescription drugs, including aspirin, Non-steroidal Anti-inflammatory Drugs (NSAIDs), vitamins, herbal and dietary supplements (including St John's Wort) within 10 days prior to the first dose of study medication.
  • In cases, where participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days
  • Subjects with exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Subjects with current enrolment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
  • Subjects with presence of Hepatitis B surface antigen (HBsAg) at screening.
  • Subjects with Positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
  • Subjects with Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention
  • Subjects with positive pre-study drug/alcohol screen
  • Subjects with positive human immunodeficiency virus (HIV) antibody test
  • Subjects with regular use of known drugs of abuse or positive urine drug test at screening or each in-house admission to the clinical research unit
  • Subjects with regular alcohol consumption within 6 months prior to screening and 5 days prior to admission defined as: An average weekly intake of > 14 units for males. One unit is equivalent to 8 gram of alcohol: a half-pint (Approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of 80 proof distilled spirits
  • Subjects with positive urinary cotinine test indicative of smoking history at screening or each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening
  • Subjects with sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03627494


Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
Layout table for location information
United States, Maryland
GSK Investigational Site Recruiting
Baltimore, Maryland, United States, 21225
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03627494     History of Changes
Other Study ID Numbers: 209275
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study
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: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Dose proportionality
Food effect
Pharmacokinetics
FTIH
Pharmacodynamics
Dose Escalation

Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Pharmaceutical Solutions