Inflammatory Bowel DiseasesPhase 1NCT02302404
A Safety and Tolerability Study of GSK2982772, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Male Subjects
A Phase 1 study testing GSK2982772 solution and GSK2982772 capsule in people with Inflammatory Bowel Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
This study is the first administration of GSK2982772 in humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of single and repeat oral doses of up to 14 days with GSK2982772 in healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Diseases
- What is being tested?
- GSK2982772 solution and GSK2982772 capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Jan 2015to 5 Mar 2016
- 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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological 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. Note: Screened subjects with laboratory values outside of the normal range may be repeated once for inclusion into the study at the discretion of the Investigator.
- Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 19 - 30 (kilogram/squared meter) kg/m^2 (inclusive).
- 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 or the follow-up visit, whichever is longer. a. Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b. Vasectomy with documentation of azoospermia; c. Male condom plus partner use of one of the contraceptive options: Contraceptive subdermal implant that meets the standard operation procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone. Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository). These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. 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 as explained by the investigator.
Who cannot join
- Alanine aminotransferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN 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).
- History of active infections within 14 days of receiving study medication.
- Average QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec) of three measures taken at least 5 minutes apart in the semi-supine position.
- History or diagnosis of obstructive sleep apnoea.
- History of a significant respiratory disorder.
Show all 26Show fewer
- History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
- Unable to refrain from prescription or non-prescription drugs, including agents active in the central nervous system, 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/or GlaxoSmithKline Medical Monitor (if needed) the medication will not interfere with the study procedures or compromise subject safety.
- History of regular alcohol consumption within 6 months of the study, defined as: For United Kingdom (UK) - an average weekly intake of >21 units for males. One unit is equivalent to 8 gram(g) of alcohol: a half-pint (approximately 240 millilitre [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Current use or history of regular tobacco- or nicotine-containing product use within 6 months of screening. Subject must have urinary cotinine levels indicative of non-smoking status at screening visit.
- Unwilling or unable to swallow multiple size 00 capsules as part of study participation
- 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 and/or Medical Monitor (if appropriate), contraindicates their participation.
- Subject received a vaccine (either live attenuated or non-live) within 30 days of randomization OR plan to receive a live attenuated vaccine within 30 days + 5 half-lives of the last dose of study medication.
- Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine > 1.6 milligram/decilitre (mg/dL) with an age appropriate glomerular filtration rate (GFR) <=60 (millilitre/minute [mL/min]/1.73 squared meter [m^2]) estimated by the CKD-EPI equation.
- A positive anti-nuclear antibody (ANA) or elevated C-reactive protein (CRP) outside of the normal reference range.
- Peripheral capillary oxygen saturation (SpO2) < 95% at room air.
- 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. As potential for and magnitude of immunosuppression with this compound is unknown, 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.
- A positive tuberculosis test.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-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.
- Part B Specific Exclusion Criteria:
- Total cholesterol >=300 mg/dL or triglycerides >=250 mg/dL. - Subjects who, in the Investigator/designee's judgment, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires (e.g., type 4 or 5 on the Columbia Suicide Severity Rating Scale [C-SSRS] in the last 5 years).
- For Cohort 5 Only (or another Cohort where Entero Test is to be performed) - History of gall bladder surgery or gall bladder removal, or history of an acute disease state (e.g., cholelithiasis) within 14 days of receiving study medication.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-centre, Randomized, Double-blind (Sponsor Unblinded), Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2982772, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Male Subjects
This study is the first administration of GSK2982772 in humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of single and repeat oral doses of up to 14 days with GSK2982772 in healthy male subjects.
This study is planned to include approximately 52 subjects and will consist of 2 parts: Part A - single ascending dose, randomized, placebo controlled, 4 way crossover. In addition to the crossover treatment periods, up to 8 subjects in cohort 2 will participate in an additional treatment period and receive GSK2982772 with a high-fat meal. Part B - repeat dose, randomized, placebo controlled, sequential-group. In both cohorts of Part A (Cohorts 1 and 2), subjects will be randomized equally (1:1:1:1) to one of 4 treatment sequences. Within each period, allocation of active to placebo treatment will be 3:1.
In all cohorts in Part B (Cohorts 3, 4 and 5) subjects will be randomized to GSK2982772 or placebo in a 3:1 ratio. If required, subjects in the additional cohorts in Part A (Cohort 6) and Part B (Cohort 7) will be randomized to GSK2982772 or placebo in a 1:1:1:1 and 3:1 ratio, respectively. The study duration, including screening and follow-up, is not expected to exceed 105 days for any subject in the study.
- Conditions
- Inflammatory Bowel Diseases
- Being tested
- GSK2982772 solution, GSK2982772 capsule, Placebo solution, Placebo capsule
- Keywords
- FTIH, pharmacodynamics, pharmacokinetics, GSK2982772, safety, Repeat dose, tolerability
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2982772 solutionDrug
Clear, colorless solution containing GSK2982772 in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg
GSK2982772 capsuleDrug
Size 00 White Opaque capsule containing GSK2982772 as white to almost white solid. Administered orally with water for dosing from 5 to 120 mg
Placebo solutionDrug
Clear, colorless solution containing placebo in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg
Placebo capsuleDrug
Size 00 White Opaque capsule containing Placebo as white to almost white solid
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg) | Experimental | Eight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through approximately 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 0.1, 0.5, 2.5, and 10mg. A sequential design will be used including approximately weekly dose escalations while allowing for a sufficient washout period. The proposed doses may be adjusted based on emerging safety and PK Receives: Drug: GSK2982772 solution; Drug: GSK2982772 capsule; Drug: Placebo solution; Drug: Placebo capsule |
| Cohort 2: GSK2982772 Single Ascending Dose (Part A) (40-240mg) | Experimental | Eight subjects will be randomized equally to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having 4 dose periods (3 active dose of GSK2982772 +1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 40, 100, 180, and 240 mg. A sequential design with weekly dose escalations and sufficient washout period will be used. The proposed doses may be adjusted based on emerging safety and PK. After the completion of the fasted treatment periods, subjects will receive a high fat meal within 30 minutes of dosing with GSK2982772 during a final treatment period. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Cohort 3: GSK2982772 Repeat Dose (Part B) | Experimental | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A data Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Cohort 4: GSK2982772 Repeat Dose (Part B) | Experimental | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in Part A or any preceding repeat dose cohorts in Part B Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Cohort 5: GSK2982772 Repeat Dose (Part B) | Experimental | Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A or any preceding repeat dose cohorts in Part B. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Cohort 6: GSK2982772 Single Ascending Dose (Part A) | Experimental | This additional cohort in Part A of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied. Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Eight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
| Cohort 7: GSK2982772 Repeat Dose (Part B) | Experimental | This additional cohort in Part B of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Receives: Drug: GSK2982772 capsule; Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of GSK2982772 as assessed by clinical monitoring and reporting of adverse events (AE) and serious adverse events (SAE)
AEs and SAEs will be collected from the start of Study Treatment until the follow-up contact
Measured: Up to approximately 105 days
Change in laboratory values after single (fed and fasted) and repeat doses of GSK2982772
Laboratory assessments will include analysis of hematology parameters, clinical chemistry, routine urinalysis, lipid panel (Part B Only) and other screening Tests
Measured: Up to approximately 105 days
Electrocardiogram (ECG) assessment after single (fed and fasted) and repeat doses of GSK2982772
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Triplicate 12-lead ECGs will be obtained pre-dose on Day 1 and Day 14 (Part B only).
Measured: Up to approximately 105 days
Change in vital signs after single (fed and fasted) and repeat doses of GSK2982772
Vital signs will be measured in semi-supine position after short period of time (e.g., 5 to 10 minutes rest) and will include systolic and diastolic blood pressure, temperature, pulse rate, pulse oximetry (SpO2), and respiratory rate. Triplicate vital signs will be obtained pre-dose on Day 1 and Day 14 (Part B only)
Measured: Up to approximately 105 days
Summary of physical examinations after single (fed and fasted) and repeat doses of GSK2982772
A complete physical examination will include assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Weight will also be measured and recorded. A brief physical examination will include assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and assessment for lymphadenopathy
Measured: Up to approximately 105 days
Secondary outcomes (5)
Composite of derived Pharmacokinetic (PK) parameters of GSK2982772 measured by AUC (0-t), AUC (0-infinity), Cmax, Tmax and t1/2,following single (fed and fasted) doses
PK parameters for GSK2982772 will include area under the blood drug concentration versus time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC [0-t]), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinity]), maximum observed blood drug concentration (Cmax), time to maximum observed blood drug concentration (Tmax), and terminal half-life (t1/2) following single (fed and fasted) doses, where data allow
Measured: Pre-dose, Days 1 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours), 2 and 3 post dose
Composite of derived blood PK parameters of GSK2982772 measured by AUC (0-t), AUC (0-infinity), AUC (0-tau), Cmax, Tmax and t1/2,following repeat doses
Derived blood PK parameters for GSK2982772 will include AUC(0-t), AUC(0-infinity), area under the concentration-time curve over the dosing interval (AUC [0-tau]), Cmax, Tmax and t1/2, following single and repeat doses
Measured: Pre-dose, Days 1 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours) , 2, 3, 4, 5, 6, 7, 14 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours), 15 and 16 post-dose
Estimation of accumulation ratio (Ro) of GSK2982772 following single and repeat doses
Ro will be calculated as the ratio of AUC(0-24) (Repeat Dose) to AUC(0-24) (Single Dose). Day 14 (Repeat Dose) will be compared with Day 1 (Single Dose) in order to estimate the accumulation ratio for each dose level
Measured: Up to Day 14 of Part B
Ratio of Plasma 4beta-hydroxycholesterol to cholesterol during pre-treatment and following repeat dosing of GSK2982772
A comparison will be made between the ratio of 4beta-hydroxycholesterol: cholesterol at baseline and on Day 14 to assess potential changes in cytochrome P450 isoform 3A4(CYP3A4) enzyme activity following GSK2982772 treatment.
Measured: Up to Day 14 of Part B
Ex-vivo GSK2982772 blood:plasma concentration ratio over a range of concentrations and % blood cell association.
Measured: Up to approximately 105 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2014 (estimated)
- Study start6 Jan 2015
- Primary completion5 Mar 2016
- Study completion5 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseasesStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinical Unit at Cambridge (Addenbrooks)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02302404
- Sponsor's protocol ID
- 200975
- Status last verified
- May 2017
- First submitted
- 27 Oct 2014
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Weisel K, Scott NE, Tompson DJ, Votta BJ, Madhavan S, Povey K, Wolstenholme A, Simeoni M, Rudo T, Richards-Peterson L, Sahota T, Wang JG, Lich J, Finger J, Verticelli A, Reilly M, Gough PJ, Harris PA, Bertin J, Wang ML. Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers. Pharmacol Res Perspect. 2017 Dec;5(6):e00365. doi: 10.1002/prp2.365.
PubMed 29226626
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-centre, Randomized, Double-blind (Sponsor Unblinded), Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2982772, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02302404
- Acronym / sponsor ID
- 200975
- Conditions
- Inflammatory Bowel Diseases
- Keywords
- FTIH, pharmacodynamics, pharmacokinetics, GSK2982772, safety, Repeat dose, tolerability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Clinical Unit at Cambridge (Addenbrooks)
- Study start
- 6 Jan 2015 (actual)
- Primary completion
- 5 Mar 2016 (actual)
- Study completion
- 5 Mar 2016 (actual)
- First posted
- 27 Nov 2014 (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 GSK2982772 in humans. The study will evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of single and repeat oral doses of up to 14 days with GSK2982772 in healthy male subjects.
This study is planned to include approximately 52 subjects and will consist of 2 parts: Part A - single ascending dose, randomized, placebo controlled, 4 way crossover. In addition to the crossover treatment periods, up to 8 subjects in cohort 2 will participate in an additional treatment period and receive GSK2982772 with a high-fat meal. Part B - repeat dose, randomized, placebo controlled, sequential-group. In both cohorts of Part A (Cohorts 1 and 2), subjects will be randomized equally (1:1:1:1) to one of 4 treatment sequences. Within each period, allocation of active to placebo treatment will be 3:1.
In all cohorts in Part B (Cohorts 3, 4 and 5) subjects will be randomized to GSK2982772 or placebo in a 3:1 ratio. If required, subjects in the additional cohorts in Part A (Cohort 6) and Part B (Cohort 7) will be randomized to GSK2982772 or placebo in a 1:1:1:1 and 3:1 ratio, respectively. The study duration, including screening and follow-up, is not expected to exceed 105 days for any subject in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg) | Experimental | Drug: GSK2982772 solution, Drug: GSK2982772 capsule, Drug: Placebo solution, Drug: Placebo capsuleEight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through approximately 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 0.1, 0.5, 2.5, and 10mg. A sequential design will be used including approximately weekly dose escalations while allowing for a sufficient washout period. The proposed doses may be adjusted based on emerging safety and PK |
| Cohort 2: GSK2982772 Single Ascending Dose (Part A) (40-240mg) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleEight subjects will be randomized equally to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having 4 dose periods (3 active dose of GSK2982772 +1 placebo dose). The subjects will fast overnight from Day -1 to Day 1 of the treatment period. Two of the 8 subjects will be randomized to the dosing on Day 1 as sentinel dosing. Assuming adequate safety in the judgment of the Principal Investigator (e.g., vital signs, ECGs, and adverse events) through 24 hours; the remaining 6 subjects may be randomized to dosing on the following day. Subjects will receive single planned doses of GSK2982772 as 40, 100, 180, and 240 mg. A sequential design with weekly dose escalations and sufficient washout period will be used. The proposed doses may be adjusted based on emerging safety and PK. After the completion of the fasted treatment periods, subjects will receive a high fat meal within 30 minutes of dosing with GSK2982772 during a final treatment period. |
| Cohort 3: GSK2982772 Repeat Dose (Part B) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleTwelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A data |
| Cohort 4: GSK2982772 Repeat Dose (Part B) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleTwelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in Part A or any preceding repeat dose cohorts in Part B |
| Cohort 5: GSK2982772 Repeat Dose (Part B) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleTwelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The subjects will fast overnight from Day -1 to Day 1 and overnight from Day 13 to Day 14. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. Once-daily dosing is planned, but twice-daily dosing may be considered based upon the exposure observed in the Part A or any preceding repeat dose cohorts in Part B. |
| Cohort 6: GSK2982772 Single Ascending Dose (Part A) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleThis additional cohort in Part A of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied. Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Eight subjects will be randomized equally (1:1:1:1) to one of the 4 placebo-controlled dose sequences with 2 subjects in each sequence and each subject having four dose periods (3 active dose of GSK2982772 + 1 placebo dose). The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. |
| Cohort 7: GSK2982772 Repeat Dose (Part B) | Experimental | Drug: GSK2982772 capsule, Drug: Placebo capsuleThis additional cohort in Part B of the study will only be conducted to allow for evaluation of additional dose levels or repeated evaluation of a dose level already studied Doses will be selected based on the safety, tolerability, and PK data from Part A and/or previous Part B cohorts. Twelve subjects will be randomized to repeat doses of GSK2982772 or placebo in a 3:1 ratio. The selection of appropriate daily doses will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts in Part B. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological 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. Note: Screened subjects with laboratory values outside of the normal range may be repeated once for inclusion into the study at the discretion of the Investigator.
- Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 19 - 30 (kilogram/squared meter) kg/m^2 (inclusive).
- 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 or the follow-up visit, whichever is longer. a. Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b. Vasectomy with documentation of azoospermia; c. Male condom plus partner use of one of the contraceptive options: Contraceptive subdermal implant that meets the standard operation procedure (SOP) effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone. Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Occlusive cap (female diaphragm or cervical/vault cap) with a vaginal spermicide (foam, gel, cream or suppository). These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. 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 as explained by the investigator.
Key exclusion criteria (26 listed)
- Alanine aminotransferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN 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).
- History of active infections within 14 days of receiving study medication.
- Average QT duration corrected for heart rate by Fridericia's formula (QTcF) > 450 milliseconds (msec) of three measures taken at least 5 minutes apart in the semi-supine position.
- History or diagnosis of obstructive sleep apnoea.
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 |
|---|---|---|
| GSK2982772 solutionClear, colorless solution containing GSK2982772 in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg | Drug | Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg) |
| GSK2982772 capsuleSize 00 White Opaque capsule containing GSK2982772 as white to almost white solid. Administered orally with water for dosing from 5 to 120 mg | Drug | Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg), Cohort 2: GSK2982772 Single Ascending Dose (Part A) (40-240mg), Cohort 3: GSK2982772 Repeat Dose (Part B), Cohort 4: GSK2982772 Repeat Dose (Part B), Cohort 5: GSK2982772 Repeat Dose (Part B), Cohort 6: GSK2982772 Single Ascending Dose (Part A), Cohort 7: GSK2982772 Repeat Dose (Part B) |
| Placebo solutionClear, colorless solution containing placebo in water with 5% ethanol (0.1mg/mL). Administered orally in required volumes for dosing less than 5mg | Drug | Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg) |
| Placebo capsuleSize 00 White Opaque capsule containing Placebo as white to almost white solid | Drug | Cohort 1: GSK2982772 Single Ascending Dose (Part A) (0.1-10mg), Cohort 2: GSK2982772 Single Ascending Dose (Part A) (40-240mg), Cohort 3: GSK2982772 Repeat Dose (Part B), Cohort 4: GSK2982772 Repeat Dose (Part B), Cohort 5: GSK2982772 Repeat Dose (Part B), Cohort 6: GSK2982772 Single Ascending Dose (Part A), Cohort 7: GSK2982772 Repeat Dose (Part B) |
Primary outcome
Safety and tolerability of GSK2982772 as assessed by clinical monitoring and reporting of adverse events (AE) and serious adverse events (SAE)
Time frame: Up to approximately 105 days
AEs and SAEs will be collected from the start of Study Treatment until the follow-up contact
Change in laboratory values after single (fed and fasted) and repeat doses of GSK2982772
Time frame: Up to approximately 105 days
Laboratory assessments will include analysis of hematology parameters, clinical chemistry, routine urinalysis, lipid panel (Part B Only) and other screening Tests
Electrocardiogram (ECG) assessment after single (fed and fasted) and repeat doses of GSK2982772
Time frame: Up to approximately 105 days
12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Triplicate 12-lead ECGs will be obtained pre-dose on Day 1 and Day 14 (Part B only).
Change in vital signs after single (fed and fasted) and repeat doses of GSK2982772
Time frame: Up to approximately 105 days
Vital signs will be measured in semi-supine position after short period of time (e.g., 5 to 10 minutes rest) and will include systolic and diastolic blood pressure, temperature, pulse rate, pulse oximetry (SpO2), and respiratory rate. Triplicate vital signs will be obtained pre-dose on Day 1 and Day 14 (Part B only)
Summary of physical examinations after single (fed and fasted) and repeat doses of GSK2982772
Time frame: Up to approximately 105 days
A complete physical examination will include assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Weight will also be measured and recorded. A brief physical examination will include assessments of the skin, lungs, cardiovascular system, abdomen (liver and spleen), and assessment for lymphadenopathy
5 secondary outcomes
Composite of derived Pharmacokinetic (PK) parameters of GSK2982772 measured by AUC (0-t), AUC (0-infinity), Cmax, Tmax and t1/2,following single (fed and fasted) doses
Time frame: Pre-dose, Days 1 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours), 2 and 3 post dose
Composite of derived blood PK parameters of GSK2982772 measured by AUC (0-t), AUC (0-infinity), AUC (0-tau), Cmax, Tmax and t1/2,following repeat doses
Time frame: Pre-dose, Days 1 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours) , 2, 3, 4, 5, 6, 7, 14 (20 and 40 minutes, 1, 1.5, 2, 3, 5, 8, 10 and 12 hours), 15 and 16 post-dose
Estimation of accumulation ratio (Ro) of GSK2982772 following single and repeat doses
Time frame: Up to Day 14 of Part B
Ratio of Plasma 4beta-hydroxycholesterol to cholesterol during pre-treatment and following repeat dosing of GSK2982772
Time frame: Up to Day 14 of Part B
Ex-vivo GSK2982772 blood:plasma concentration ratio over a range of concentrations and % blood cell association.
Time frame: Up to approximately 105 days
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 9 May 2017.
- Derived from this study: PubMed 29226626Weisel K, Scott NE, Tompson DJ, Votta BJ, Madhavan S, Povey K, Wolstenholme A, Simeoni M, Rudo T, Richards-Peterson L, Sahota T, Wang JG, Lich J, Finger J, Verticelli A, Reilly M, Gough PJ, Harris PA, Bertin J, Wang ML. Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers. Pharmacol Res Perspect. 2017 Dec;5(6):e00365. doi: 10.1002/prp2.365.
- Results for study 200975 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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 GSK2982772 solution and GSK2982772 capsule in people with Inflammatory Bowel Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.
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 5 inclusion and 26 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 9 May 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 Kingdom. 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 GSK2982772 as assessed by clinical monitoring and reporting of adverse events (AE) and serious adverse events (SAE) (time frame: Up to approximately 105 days). The study lists 5 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 NCT02302404, 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 9 May 2017; AzTrials last refreshed its copy on 8 Nov 2026.