A Study to Investigate the Pharmacokinetics (PK) of Modified Release (MR) Prototype Coated Tablet Formulations of GSK2982772

NCT03649412 | Completed Phase 1 Results

• 2 other identifiers: 2092612018-002370-48
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Previous clinical studies of immediate release (IR) formulations of GSK2982772 resulted in a high peak to trough ratio of GSK2982772. Additionally, the short half-life for GSK2982772 (approximately 2 to 3 hours) necessitates twice a daily (BID) or thrice daily (TID) dosing of an IR formulation. As a result, MR formulations using a polymer matrix approach with minitablets in capsule and MR tablet formulations were investigated. The emerging PK data of the MR formulations investigated to date have demonstrated that a once daily (QD) PK profile can be achieved in the fasted state but the polymer matrix formulation is susceptible to food effects when administered with a high fat breakfast. The purpose of this study is to evaluate MR prototype coated tablet formulations. This study will evaluate the PK of MR prototype coated tablet formulations of GSK2982772. The study is divided into two parts; Part A and Part B. The MR tablet coating used in Part A and the initial periods of Part B will have an aperture drilled into the enteric coating of either side of the tablet. This allows some drug release to commence in the stomach whilst providing controlled release throughout the gastrointestinal (GI) tract. In Part B only, a new investigational medicinal product (IMP) will be manufactured to allow comparison of the tablet coating either with apertures (i.e., drilled) or without apertures (i.e., full coat/non drilled). Part A will be a 6-period, 6-way fixed sequence design, up to 4 MR tablet prototype coated formulations will be evaluated in fasted state at 240 milligrams (mg). Periods 1, 2 and 3 will evaluate MR1, IR tablet and MR2 respectively. Periods 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 to 3. In addition, the impact of food (high fat meal, standard breakfast or administration 30 or 60 minutes before a standard breakfast) on selected MR prototype coated tablet formulations may also be evaluated in Period 4, 5 or 6 of Part A. Each inpatient period for MR regimens (Periods 1, 3, 4 to 6) will consist of 4 days and 3 nights, and the inpatient period for the IR tablet (Period 2) will consist of 3 days and 2 nights. There will be a minimum washout of 7 days between doses, and a follow-up visit will occur at 7 to 9 days after the last study treatment. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses and with or without apertures in the tablet coatings. There will be an interim review after each period 1 to 5 of Part B to select the dose level, formulation and prandial status for each subsequent period. An interim data review after Part B Period 6 will determine if optional Period 7 is required and the dose level, dosing time (morning or evening), formulation and prandial status for that period. Each inpatient period will consist of a 4-day and 3-night with a minimum of 7 days washout between doses. A follow-up visit will occur at 7 to 9 days after the last study treatment. Approximately 33 subjects will be enrolled in the study. The total duration for Part A will be approximately 10-12 weeks and 10-14 weeks for Part B (including screening period of approximately 4 weeks).

Conditions

Autoimmune Diseases

Keywords

Tablet formulation; Sequence; Immediate release; Pharmacokinetic

Outcome Measures

Primary Outcomes (41)

• Part A: Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 240 mg in IR Formulation

  Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were analyzed using standard non-compartmental analysis. Participants in the 'Safety Population (all participants who received at least one dose of study treatment)' for whom a PK sample was obtained and analyzed were part of PK Population.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose

• Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose

• Part A: Maximum Observed Concentration (Cmax) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Concentration at 24 Hours Post-dose (C24h) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.

  24 hours post-dose

• Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.

  24 hours post-dose

• Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.

  24 hours post-dose

• Part A: Time to Cmax (Tmax) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Terminal Half-life (t1/2) of GSK2982772 240 mg for IR Formulation

  Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose

• Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation

  Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours

• Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours

• Part B: AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for AUC(0-inf). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for AUC(0-t). PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: Cmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose post-dose

• Part B: C24h of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis.

  24 hours post-dose

• Part B: Tmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: t1/2 of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast

  Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Relative Bioavailability in Fed Versus Fasted Conditions (FrelFE) Based on AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation

  Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: FrelFE Based on AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation

  Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR Fed/Geometric mean of AUC(0-t) of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: FrelFE Based on Cmax of GSK2982772 for MR Coated Tablet Formulation

  Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fed/Geometric mean of Cmax of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: FrelFE of GSK2982772 Based on AUC(0-inf) for MR Coated Tablet Formulation in Fed vs Fasted State

  Blood samples were collected at indicated time points for analysis of FrelFE based on AUC(0-inf) of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: FrelFE of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fed vs Fasted State

  Blood samples were collected at indicated time points for analysis of FrelFE based on AUC (0-t) of GSK2982772. FrelFE for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MR Fed/ Geometric mean of AUC (0-t) of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: FrelFE of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fed vs Fasted State

  Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. FrelFE for Cmax was calculated as Geometric mean of Cmax of MR Fed/ Geometric mean of Cmax of MR Fasted multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: Frel of GSK2982772 Based on AUC (0-inf) for MR Coated Tablet Formulation in Fasted State

  Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC (0-inf) of GSK2982772. Frel (dose) for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MR formulation (test dose) Fasted/ Geometric mean of AUC (0-inf) of MR Fasted formulation (reference dose) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: Frel of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fasted State

  Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-t) of GSK2982772. Frel (dose) for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR formulation (test dose) Fasted/ Geometric mean of AUC(0-t) of MR Fasted formulation (reference dose) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part B: Frel of GSK2982772 Based on AUC (0-24) for MR Coated Tablet Formulation in Fasted State

  Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-24) of GSK2982772. Frel (dose) for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR formulation (test dose) Fasted/Geometric mean of AUC(0-24) of MR Fasted formulation (reference dose) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose

• Part B: Frel of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fasted State

  Blood samples were collected at indicated time points for analysis of Frel dose. Frel for Cmax was calculated as Geometric mean of Cmax of MR formulation (test) Fasted/ Geometric mean of Cmax of MR Fasted Formulation (reference dose) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 240 mg

  Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC(0-inf) of GSK2982772 in fasted state. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR formulation (test) Fasted/ Geometric mean of AUC(0-inf) of Fasted of IR Formulation (reference) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose

• Part A: Frelformulation Based on AUC (0-t) of GSK2982772 for MR Coated Tablet Formulation (240 mg)

  Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC (0-t) was calculated as Geometric mean of AUC(0-t) of MR Fasted formulation (test) / Geometric mean of AUC(0-t) of Fasted of IR Formulation (reference) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours

• Part A: Frelformulation Based on AUC(0-24) of GSK2982772 for MR Coated Tablet Formulation (240 mg)

  Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR Fasted formulation (test) / Geometric mean of AUC(0-24) of Fasted of IR Formulation (reference) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours

• Part A: Frelformulation Based on Cmax of GSK2982772 for MR Coated Tablet Formulation (240 mg)

  Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 in fasted state. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fasted formulation (test) / Geometric mean of Cmax of Fasted Formulation of IR formulation (reference) multiplied by 100.

  Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours

Secondary Outcomes (14)

• Part A: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Day 67

• Part A: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria

  Up to Day 67

• Part A: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria

  Up to Day 67

• Part A: Number of Participants With Abnormal Urinalysis Dipstick Results

  Day 2 (post-dose)

• Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in IR Formulation

  Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours

Study Arms (2)

Subjects in Part A

EXPERIMENTAL

Subjects in Part A will receive GSK2982772 MR (Period 1, 3, 4, 5 and 6) and GSK2982772 IR (Period 2).

Drug: GSK2982772 Modified Release; Drug: GSK2982772 Immediate Release

Subjects in Part B

EXPERIMENTAL

Subjects in Part B will receive GSK2982772 MR.

Drug: GSK2982772 Modified Release

Interventions

GSK2982772 Modified Release DRUG

GSK2982772 MR will be available as MR prototype coated tablet with unit dose strength of 240 mg in Part A. In Part B, GSK2982772 MR prototype coated tablet with unit dose strength of 120 mg (may be changed following interim review of Part B) will be administered by subjects. GSK2982772 MR will be administered orally with 240 milliliter (mL) of water.

Subjects in Part A; Subjects in Part B

GSK2982772 Immediate Release DRUG

In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water

Subjects in Part A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject at the time of participation must be 18 to 65 years of age.
• Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Body weight greater than or equal to 50 kilogram (kg) and body mass index within the range 19.0 to 32.0 kg per squared meter (kg/m\^2) (inclusive).
• Male or female subjects where male subjects are eligible to participate if they agree to the following during the intervention period until completion of the final follow up visit after the last dose of study treatment; refrain from sperm donation; plus either be abstinent from heterosexual or homosexual 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 like use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant; agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
• Capable of giving an Informed Consent.

You may not qualify if:

• History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
• Any history of suicidal behavior within the past 6 months or any history of attempted suicide in subject's lifetime.
• History of clinically significant psychiatric disorders as judged by the investigator. Depression requiring treatment in the last 2 years.
• History of herpes zoster (shingles) reactivation.
• History or diagnosis of obstructive Sleep Apnea.
• History of a significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
• History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
• A positive diagnostic tuberculosis (TB) test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative.
• History of GI surgery (with exception of appendectomy).
• History of cholecystectomy or gall stones.
• Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever is allowed unless it is active.
• Alanine transaminase (ALT) greater than 1.5 times upper limit of normal (ULN).
• Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage of total).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
• Corrected QT interval (QTcF) greater than 450 milliseconds (msec).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Quotient Sciences: collaborator

Study Sites (1)

GSK Investigational Site

Nottingham, NG11 6JS, United Kingdom

Location

Related Publications (1)

• Tompson D, Whitaker M, Pan R, Johnson G, Fuller T, Zann V, McKenzie L, Abbott-Banner K, Hawkins S, Powell M. Development of a Once-Daily Modified-Release Formulation for the Short Half-Life RIPK1 Inhibitor GSK2982772 using DiffCORE Technology. Pharm Res. 2022 Jan;39(1):153-165. doi: 10.1007/s11095-021-03124-7. Epub 2022 Jan 5.

  PMID: 34988780 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

GSK2982772

Condition Hierarchy (Ancestors)

Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: There will be no masking as this is an open-label study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A will be a 6-period, 6-way fixed sequence design, in which up to 4 MR tablet prototype coated formulation will be evaluated, following single dose administration (240 mg) in fasted or fed state. There will be a minimum 7-day washout between doses. Part B of the study is optional. Following the final period of Part A, there will be an interim review to determine whether to proceed with optional Part B, and if so, the formulations and tablet strengths to be investigated in Part B. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses.

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 28, 2018
• Study Start: September 26, 2018
• Primary Completion: May 7, 2019
• Study Completion: May 7, 2019
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Data Sharing

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

Locations

GB (1)