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Healthy VolunteersPhase 1NCT02742766

Safety, Tolerability and Preliminary Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeat Oral Doses of GSK3008356 in Healthy and Obese Subjects

A Phase 1 study testing GSK3008356 in people with Healthy Volunteers, run by GlaxoSmithKline at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is a phase I, randomized, placebo-controlled, double-blind (sponsor unblind), three part study. The primary objective of the study is to characterize the safety, and tolerability of GSK3008356 single dose, 14 daily repeat doses in healthy subjects and 28 daily repeat doses in obese subjects. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
GSK3008356
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
104 participants
Where
1 siteAustralia
Study dates
14 Mar 2016to 16 Jun 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • For Part 1 and Part 2: Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • For Part 3: Obese subjects may have chronic disease not specifically excluded and not requiring chronic medication for treatment and are otherwise healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, 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.
  • Body weight >=50 kilograms (kg)
  • For Part 1 and Part 2 body mass index (BMI) 19-25 kilogram per meter square (inclusive)
  • For Part 3 BMI >=30 kilogram per meter square
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  • Males or Females of non-childbearing potential as follows: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until at least five half-lives of study medication after the last dose of study medication.
  • Vasectomy with documentation of azoospermia.
  • Male condom plus partner use of one of the following contraceptive options: Contraceptive subdermal implant; Intrauterine device or intrauterine system; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches
  • Males or Females of non-childbearing potential as follows: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and the following condition applies:
  • Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-international units per milliliter (MlU/ml) and estradiol < 40 picograms (pg) per ml (<147 picomoles per liter (pmol/L) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will not be allowed.
  • The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Who cannot join

  • Alanine aminotransferase (ALT) and bilirubin >1.5 times upper limit of normal (isolated bilirubin >1.5 times upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • QTcF >450 millisecond (msec)
  • Current or chronic history of gastrointestinal illness or conditions interfering with normal gastrointestinal anatomy or motility. Examples include gastrointestinal bypass surgery, cholecystectomy, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, irritable bowel syndrome (IBS), or celiac sprue.
  • Use of 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 drug, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. By exception, subject may take acetaminophen (<=2 grams per day) up to 48 hours prior to the first dose of study drug.
  • Subjects should 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 until after the final dose.
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  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 standard drinks. One standard drink is equivalent to 10 grams of alcohol: 285 milliliter (mL) of beer, 100 mL of wine or 30 mL of 40% alcohol by volume distilled spirits.
  • For Part 1 and Part 2, urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • 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 Medical Monitor, contraindicates their participation.
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 750 mL within 90 day period.
  • 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: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • GSK Investigational Site

    Melbourne, Victoria, 3004

Other trials in Australia

About this study

Official title: A Phase I, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Three Part Study to Evaluate the Safety, Tolerability, Preliminary PK and PD of Single and Repeat Oral Doses of GSK3008356 in Healthy Subjects and Obese Subjects

This study is a phase I, randomized, placebo-controlled, double-blind (sponsor unblind), three part study. The primary objective of the study is to characterize the safety, and tolerability of GSK3008356 single dose, 14 daily repeat doses in healthy subjects and 28 daily repeat doses in obese subjects. The study has three parts. Part 1, will be a single and multiple-dose, dose-rising study in healthy subjects. Part 2, will be a 14-day, repeat-dose, dose-rising study in healthy subjects, and part 3 will be a 28-day, repeat-dose study in obese subjects. For Parts 1 and 2, data from prior doses cohorts will be available prior to escalation decisions. Data from Parts 1 and 2 will be available prior to initiation of the three parallel cohorts in Part 3. A dose escalation meeting will be held to review these data and document the decision to proceed as planned or make any alterations in dosing, if indicated. Part 1, Part 2 and Part 3 study will have approximately 88, 24 and 30 subjects, respectively.

Being tested
GSK3008356, Placebo
Keywords
Dose escalation study, Safety, Pharmacodynamics, Pharmacokinetics, GSK3008356, Tolerability

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3008356Drug

    This intervention is available as 0.5, 1, 5, and 25 mg white oral tablet. The formulation will be used to administer dose of 5 mg, 10 mg, 30 mg, 45 mg, 75 mg, 90 mg, 125 mg, 180 mg, 200 mg, and 250 mg total daily dose during the study.

  • PlaceboDrug

    This intervention is available as white oral tablet. The formulation will be used as a matching placebo for GSK3008356 during the study.

Study groups in NCT02742766
Study groupRoleWhat they receive
Part 1 - GSK3008356 single dose and multiple dosesExperimentalHealthy subjects will receive GSK3008356 in morning as single dose or multiple doses of 5 milligrams (mg), 10 mg, 30 mg,45 mg, 75 mg, 90 mg, 125, 180 mg, 200 mg, 250 mg total daily dose or matching placebo in eleven sequential cohorts while receiving a standard fat meal. The initial dosing for the first cohort will be staggered so that 2 subjects will be dosed as sentinel subjects. Provided there are no safety concerns, the remainder of the subjects scheduled for the cohort may be dosed. Eight subjects will be enrolled in each cohort.
Receives: Drug: GSK3008356; Drug: Placebo
Part 2 - GSK3008356 14 day repeat doseExperimentalHealthy subjects will receive GSK3008356 or matching placebo, as 14 daily doses in the three sequential cohorts. Subjects in cohort 1 will receive their daily dose in morning, while subjects in cohort 2 and cohort 3 will receive their daily dose in evening. In all the three cohorts, Day 1 and day 14 dosing will occur while receiving a standard fat meal in morning. Eight subjects will be enrolled in each cohort.
Receives: Drug: GSK3008356; Drug: Placebo
Part 3 - GSK3008356 28 day repeat doseExperimentalObese subjects will receive GSK3008356 or matching placebo, as 28 daily doses in the three parallel cohorts. Cohort 1 will evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as morning doses. Cohorts 2 and 3 will evaluate 2 dose strengths (1 per cohort) of GSK3008356 (or matching placebo) administered in the evening. Ten subjects will be enrolled in each cohort.
Receives: Drug: GSK3008356; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Number of Participants With Abnormal Findings in Physical Examinations

    A complete physical examination included assessment of the cardiovascular, respiratory, gastrointestinal, dermatologic and neurological systems, height, and weight. Height was measured and recorded only at screening. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Weight was recorded with the brief physical exam, but was not part of the brief physical exam. Number of participants with abnormal findings in physical examinations in Part 1 are presented.

    Measured: Up to Day 8

  2. Part 1: Number of Participants With Vital Signs of Potential Clinical Concern

    Vital signs included systolic and diastolic blood pressure and pulse rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring.

    Measured: Up to Day 8

  3. Part 1: Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern

    Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.

    Measured: Up to Day 4

  4. Part 1: Number of Participants With Clinically Significant Findings During Cardiac Monitoring

    Continuous lead II cardiac telemetry or cardiac monitoring was performed on Day 1. Number of participants with clinically significant findings during cardiac monitoring in Part 1 are presented.

    Measured: Day 1

  5. Part 1: Number of Participants With Laboratory Values of Potential Clinical Concern

    Hematology parameters included hematocrit, hemoglobin, platelets, white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells (RBC) and reticulocytes. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, uric acid, total protein, total and direct bilirubin, albumin, calcium, bile acids, chloride, creatinine, glucose (fasting/non-fasting), potassium, sodium and total carbon dioxide/bicarbonate. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine (WBC, RBC and casts) within 120 minutes of collection.

    Measured: Up to Day 8

  6. Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury and impaired liver function.

    Measured: Up to Day 8

  7. Part 2: Number of Participants With Abnormal Findings in Physical Examination

    A complete physical examination included assessment of the cardiovascular, respiratory, gastrointestinal, dermatologic and neurological systems, height, and weight. Height was measured and recorded only at screening. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Weight was recorded with the brief physical exam, but was not part of the brief physical exam. Number of participants with abnormal findings in physical examinations in Part 2 are presented.

    Measured: Up to Day 22

  8. Part 2: Number of Participants With Vital Signs of Potential Clinical Concern

    Vital signs included systolic and diastolic blood pressure and pulse and was measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring.

    Measured: Up to Day 22

  9. Part 2: Number of Participants With 12-lead ECG Values of Potential Clinical Concern

    Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QTcF. Number of participants with 12-lead ECG values of potential clinical concern in Part 2 are presented.

    Measured: Up to Day 17

  10. Part 2: Number of Participants With Clinically Significant Findings During Cardiac Monitoring

    Continuous lead II cardiac telemetry or cardiac monitoring was performed on Day 1. Number of participants with clinically significant findings during cardiac monitoring in Part 2 are presented.

    Measured: Day 1 (Pre-dose to 4 hours post dose)

  11. Part 2: Number of Participants With Laboratory Values of Potential Clinical Concern

    Hematology parameters included hematocrit, hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells and reticulocytes. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, uric acid, total protein, total and direct bilirubin, albumin, calcium, bile acids, chloride, creatinine, glucose (fasting/non-fasting), potassium, sodium and total carbon dioxide/bicarbonate. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination (within 120 minutes of collection).

    Measured: Up to Day 22

  12. Part 2: Number of Participants With AE and SAE

    AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury and impaired liver function.

    Measured: Up to Day 22

  13. Part 3: Number of Participants With Abnormal Findings in Physical Examination

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Up to Day 36

  14. Part 3: Number of Participants With Vital Signs of Potential Clinical Concern

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Up to Day 36

  15. Part 3: Number of Participants With 12-lead ECG Values of Potential Clinical Concern

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Up to Day 31

  16. Part 3: Number of Participants With Clinically Significant Findings During Cardiac Monitoring

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Day 1 (Pre-dose to 4 hours post-dose)

  17. Part 3: Number of Participants With Laboratory Values of Potential Clinical Concern

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Up to Day 36

  18. Part 3: Number of Participants With AE and SAE

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Up to Day 36

Secondary outcomes (28)

  1. Part 1: Area Under the Concentration-time Curve (AUC) Extrapolated to Infinity (AUC[0 to Inf]), AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0 to t]) and AUC From Time Zero to 24 Hour (AUC[0 to 24])

    Blood samples for pharmacokinetic (PK) analysis of GSK3008356 were collected at the indicated time points.

    Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

  2. Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3008356

    Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

    Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post dose on Day 1 and 36, 48, and 72 hours post-dose

  3. Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of GSK3008356 and Apparent Terminal Half-life (t1/2) of GSK3008356

    Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

    Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post dose on Day 1 and 36, 48, and 72 hours post-dose

  4. Part 1: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of GSK3008356

    Urine samples for PK analysis of GSK3008356 were collected at the indicated time points.

    Measured: Pre-dose and over the post-dose intervals 0 to 12 hours and 12 to 24 hours

  5. Part 1: Renal Clearance of Drug From Plasma (CLr) of GSK3008356

    Urine samples for PK analysis of GSK3008356 were collected at the indicated time points.

    Measured: Pre-dose and over the post-dose intervals 0 to 12 hours and 12 to 24 hours

  6. Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC

    Dose proportionality was assessed from the AUC (0 to t) and AUC (0 to inf) obtained from multiple cohorts in Part 1. The dose proportionality was assessed using a power model on logarithmic transformation of AUC with the logarithmic transformation of dose as the single covariate in the linear regression. Point estimates and 90% confidence interval are presented.

    Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

  7. Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg vs. 200 mg After Single Dose Administration Based on Cmax

    Dose proportionality was assessed from the Cmax obtained from multiple cohorts in Part 1. The dose proportionality was assessed using a power model on logarithmic transformation of Cmax, with the logarithmic transformation of dose as the single covariate in the linear regression. For Cmax, only a single dose group from Cohort 1 to Cohort 6 was considered since other cohorts are multiple dosing where Cmax is so different from that of single dose group. Data for Cohort A5 vs. Cohort A1 is presented, Point estimates and 90% confidence interval are presented.

    Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

  8. Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356

    Preliminary pharmacodynamics of GSK3008356 was evaluated by assessing the postprandial triglyceride levels at the indicated time points. Corrected triglyceride value (Day 1) at each nominal sampling time point was defined as the corresponding post dose value by adding the following value: Part 1 Day 1 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 1 (1 hour + 2 hour)/2). Mean triglyceride levels are presented.

    Measured: Day 1 at 1,2,3,4,5,6,7,8,9,12 hours post-dose

  9. Part 2: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the End of Dosing Interval (AUC[0 to Tau]) of GSK3008356 on Day 1 and Day 14

    Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

  10. Part 2: Cmax of GSK3008356 on Day 1 and Day 14

    Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

  11. Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14

    Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

  12. Part 2: Ae of GSK3008356 on Day 14

    Urine samples (urine concentrations or volumes) were not collected for the Part 2 of the study.

    Measured: Pre-dose and 24 hours post-dose on Day 14

  13. Part 2: CLr of GSK3008356 on Day 14

    Urine samples (urine concentrations or volumes) were not collected for the Part 2 of the study.

    Measured: Pre-dose and 24 hours post-dose on Day 14

  14. Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC

    Dose proportionality was assessed from Day 1 and Day 14 AUC (0 to tau) obtained from multiple cohorts in Part 2. The dose proportionality was assessed using a power model on logarithmic transformation of AUC, with the logarithmic transformation of dose as the single covariate in the linear regression. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose. Point estimates and 90% confidence interval are presented.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

  15. Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on Cmax

    The dose proportionality was assessed using a power model on logarithmic transformation of Cmax, with the logarithmic transformation of dose as the single covariate in the linear regression. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose. Point estimates and 90% confidence interval are presented for Day 1 and Day 14 of Part 2.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post-dose

  16. Part 2: Observed Accumulation Ratio of GSK3008356

    Observed accumulation ratio based on AUC(0- tau) is (Ro), and based on Cmax is (RCmax). Ro was calculated as the ratio [AUC0-tau on the final day (Day 14)]/[ AUC0-tau on Day 1] and Rcmax was calculated as the ratio [Cmax on the final day (Day 14)]/[Cmax on Day 1]. Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

    Measured: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

  17. Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing

    Ctrough is the observed concentration at the end of a dosing interval, immediately before next administration. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

    Measured: Pre-dose on Days 2, 4, 5, 6, 12, 13, 14 and the 24 hours post-dose on Day 14

  18. Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356

    Preliminary pharmacodynamics of GSK3008356 was evaluated by assessing the postprandial triglyceride levels at the indicated time points. Corrected TG value (Day 1 and Day 14) at each nominal sampling time point defined as the corresponding post dose value by adding the following value: Part 2 Day 1 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 1 (1 hour + 2 hour)/2); Part 2 Day 14 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 14 (1 hour + 2 hour)/2). Mean triglyceride levels are presented.

    Measured: Day 1 (1, 2, 3, 4, 5, 6, 7, 8, 9 and 12 hours post-dose) and Day 14 (1, 2, 3, 4, 5, 6, 7, 8, 9 and 12 hours post-dose)

  19. Part 3: AUC (0-tau) of GSK3008356 on Day 1 and Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  20. Part 3: Cmax of GSK3008356 on Day 1 and Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  21. Part 3: Tmax of GSK3008356 on Day 1 and Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  22. Part 3: t1/2 of GSK3008356 on Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, 24, 36, 48, and 72 hours post-dose on Day 28

  23. Part 3: Ae of GSK3008356 on Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Day 28 in each cohort

  24. Part 3: CLr of GSK3008356 on Day 28

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Day 28 in each cohort

  25. Part 3: Dose Proportionality of GSK3008356

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  26. Part 3: Observed Accumulation Ratio of GSK3008356

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  27. Part 3: Ctrough to Assess Steady State of GSK3008356 Following 28-day Repeat Dosing

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

  28. Part 3: Postprandial Triglyceride Levels Following 28-day Repeat Dosing of GSK3008356 in Obese Participants

    Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

    Measured: Day -1, Day 1, and Day 28 in cohort 1, and Day 1, Day 2, and Day 28 in cohorts 2 and 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2016 (estimated)
  2. Study start14 Mar 2016
  3. Primary completion16 Jun 2017
  4. Study completion16 Jun 2017

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02742766
Sponsor's protocol ID
204856
Status last verified
Jul 2019
First submitted
10 Mar 2016
Last updated
24 Jul 2019
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Okour M, Gress A, Zhu X, Rieman D, Lickliter JD, Brigandi RA. First-in-Human Pharmacokinetics and Safety Study of GSK3008356, a Selective DGAT1 Inhibitor, in Healthy Volunteers. Clin Pharmacol Drug Dev. 2019 Nov;8(8):1088-1099. doi: 10.1002/cpdd.691. Epub 2019 Apr 5.

    PubMed 30950565

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3008356 in people with Healthy Volunteers, run by GlaxoSmithKline at 1 site in Australia.

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 13 inclusion and 15 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 24 Jul 2019. 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 Australia. 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?

Yes. Results are posted in the registry (first posted 15 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Part 1: Number of Participants With Abnormal Findings in Physical Examinations (time frame: Up to Day 8). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02742766, which also lists 1 linked publication.

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 24 Jul 2019.

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