En undersøgelse for at evaluere effektiviteten og sikkerheden af GSK3915393 hos deltagere med idiopatisk lungefibrose (IPF)
Et fase 2, randomiseret, dobbeltblindt, placebokontrolleret, parallelt gruppestudie (TRANSFORM) for at evaluere effektiviteten og sikkerheden af GSK3915393 hos deltagere med idiopatisk lungefibrose (IPF)
Idiopathic Pulmonary Fibrosis is a chronic lung disease which causes scarring of the lungs and difficulty in breathing. GSK3915393 is a new medicine, which is being tested in participants with IPF for the first time. The study will assess the safety and effectiveness of GSK3915393 in IPF participants.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Buenos Aires, Argentina, C1426ABP
- GSK Investigational Site
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Ciudad Autonoma de Bueno, Argentina, C1207AAP
- GSK Investigational Site
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Florida, Argentina, B1602DQD
- GSK Investigational Site
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La Plata, Argentina, 1900
- GSK Investigational Site
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Mendoza, Argentina, M5500CCG
- GSK Investigational Site
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Rosario, Argentina, S2000DBS
- GSK Investigational Site
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1M9
- GSK Investigational Site
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1B 3V6
- GSK Investigational Site
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Ontario
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Ajax, Ontario, Canada, L1S 2J5
- GSK Investigational Site
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Hamilton, Ontario, Canada, L8N 4A6
- GSK Investigational Site
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Quebec
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Trois-Rivières, Quebec, Canada, G8T 7A1
- GSK Investigational Site
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Edinburgh, Det Forenede Kongerige, EH16 4SA
- GSK Investigational Site
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Leeds West Yorkshire, Det Forenede Kongerige, LS9 7TF
- GSK Investigational Site
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London, Det Forenede Kongerige, SW3 6HP
- GSK Investigational Site
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California
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Newport Beach, California, Forenede Stater, 92663
- GSK Investigational Site
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Florida
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Jacksonville, Florida, Forenede Stater, 32224
- GSK Investigational Site
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St. Petersburg, Florida, Forenede Stater, 33704
- GSK Investigational Site
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109-5360
- GSK Investigational Site
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- GSK Investigational Site
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New York
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New York, New York, Forenede Stater, 10065
- GSK Investigational Site
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North Carolina
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Wilmington, North Carolina, Forenede Stater, 28401
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19140
- GSK Investigational Site
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37204
- GSK Investigational Site
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Texas
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Cypress, Texas, Forenede Stater, 77429
- GSK Investigational Site
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La Tronche, Frankrig, 38700
- GSK Investigational Site
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Paris, Frankrig, 75018
- GSK Investigational Site
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Pessac, Frankrig, 33604
- GSK Investigational Site
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Rennes, Frankrig, 35000
- GSK Investigational Site
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Rouen, Frankrig, 76000
- GSK Investigational Site
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Toulouse, Frankrig, 31059
- GSK Investigational Site
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Eindhoven, Holland, 5623 EJ
- GSK Investigational Site
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Rotterdam, Holland, 3015 CE
- GSK Investigational Site
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Catania, Italien, 95123
- GSK Investigational Site
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Monza MB, Italien, 20900
- GSK Investigational Site
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Naples, Italien
- GSK Investigational Site
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Padova, Italien, 35128
- GSK Investigational Site
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Perugia, Italien, 06132
- GSK Investigational Site
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Pisa, Italien, 56124
- GSK Investigational Site
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Roma, Italien, 00168
- GSK Investigational Site
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Sassari, Italien, 07100
- GSK Investigational Site
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Torrette AN, Italien
- GSK Investigational Site
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Bialystok, Polen, 15-044
- GSK Investigational Site
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Lodz, Polen, 90-153
- GSK Investigational Site
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Poznan, Polen, 60-569
- GSK Investigational Site
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Barcelona, Spanien
- GSK Investigational Site
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Barcelona, Spanien, 08907
- GSK Investigational Site
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Madrid, Spanien, 28006
- GSK Investigational Site
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Madrid, Spanien, 28007
- GSK Investigational Site
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Oviedo, Spanien, 33011
- GSK Investigational Site
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Pozuelo de AlarcOn Madr, Spanien, 28223
- GSK Investigational Site
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Santander, Spanien, 39011
- GSK Investigational Site
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Seville, Spanien, 41013
- GSK Investigational Site
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Essen, Tyskland, 45293
- GSK Investigational Site
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Hanover, Tyskland, 30173
- GSK Investigational Site
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Heidelberg, Tyskland, 69126
- GSK Investigational Site
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Wuppertal, Tyskland, 42283
- GSK Investigational Site
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Participants with IPF diagnosed within 5 years prior to screening based on the applicable American Thoracic Society (ATS)/ European Respiratory Society (ERS)/ Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) Guideline at the time of diagnosis.
- Centrally read chest High Resolution Computed Tomography (HRCT) obtained at screening or historical HRCT obtained within 12 months of screening that is consistent with Usual interstitial pneumonia (UIP) or probable UIP (if indeterminate HRCT finding, IPF may be confirmed locally by historical biopsy).
- FVC greater than or equal to (>=) 45 percent (%) of predicted normal.
- Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) >=25% of predicted normal corrected for hemoglobin (Hb).
- Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC >=0.7.
- If receiving antifibrotics must be on stable dose of nintedanib or pirfenidone for at least 12 weeks prior to screening.
- If not receiving approved antifibrotics (pirfenidone or nintedanib) there should be a valid reason for this, such as previous failure, contraindications, failure to meet national or regional eligibility criteria for anti-fibrotic treatment, or participant choice.
- If not currently receiving pirfenidone or nintedanib, participant must have stopped pirfenidone or nintedanib for at least 4 weeks prior to screening.
- Body weight >=40 kilogram (kg) and body mass index within the range 18.5-35 kilogram per meter square (kg/m^2) (inclusive).
- A female participant is eligible to participate if a woman of nonchildbearing potential (WONCBP)
- Capable of giving signed informed consent
Exclusion Criteria:
- Participants with Interstitial Lung Disease (ILD) associated with other known causes.
- Diagnosis of sarcoidosis or any systemic autoimmune disease (including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus and rheumatoid arthritis).
- Acute IPF exacerbation within 6 months prior to screening and/or during the screening period (investigator-determined).
- Clinically significant non-parenchymal lung disease (e.g., asthma, chronic obstructive pulmonary disease, cavitary or pleural diseases) at screening.
- Diagnosis of severe pulmonary hypertension (investigator-determined)
- Extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT.
- History of previous lung transplant or recent major surgery (investigator-determined) within 12 weeks prior to screening or planned during the trial period. Registration on a transplant waiting list is allowed.
- Clinically significant respiratory tract infection (e.g., active tuberculosis, infectious pneumonia, Corona virus disease 2019 [COVID-19]) requiring treatment within 4 weeks prior to and/or during the screening period.
- Cigarette smoking (including e-cigarettes) either current or within 3 months before screening.
- Current or chronic liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) greater than (>) 2x Upper Limit of Normal (ULN) and bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than (<) 35% at screening).
- Clinically significant abnormalities detected on ECG of either rhythm or conduction, a Corrected QT interval (QTc) >450 millisecond (msec) or QTc > 480msec for participants with a bundle branch block and/or a pacemaker who are actively ventricularly pacing during the screening ECG.
- Participants with pacemakers who are not pacing at the time of the screening ECG should have a non-paced QTc <450 msec.
Prior/Concomitant Therapy-
- Simultaneous use of pirfenidone and nintedanib at screening.
- Received systemic corticosteroids equivalent to prednisone >10 milligrams/day or equivalent within 2 weeks of screening period.
- Use of any of the following therapies within 4 weeks prior to screening and during the screening period or planned during the study:
- Immunomodulatory therapies, including but not limited to azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide, imatinib, Tumour Necrosis Factor -Alpha (TNF- α) inhibitors.
- Medications that are under investigation for the treatment of IPF including inhaled treprostinil and Phosphodiesterase-4 (PDE-4) inhibitors. Symptomatic cough therapies are allowed.
- Current use of systemic strong and moderate inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.
- Current use of systemic CYP3A4 substrates that have a narrow therapeutic index that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: GSK3915393
Participants received GSK3915393 80 milligrams (mg), orally, twice daily for 26 weeks. |
GSK3915393 was administered. |
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Placebo komparator: Placebo
Participants received matching placebo, orally, twice daily for 26 weeks. |
Placebo was administered. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Absolute Change From Baseline in Forced Vital Capacity (FVC) at Week 26
Tidsramme: Baseline (Day 1) and Week 26
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Forced vital capacity (FVC) is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. The maximum of triplicate FVC for each participant was used for calculations. Baseline was defined as the last non-missing value/assessment prior to the first dose of study treatment on Day 1. Change from Baseline (CFB) in FVC at Week 26 was calculated for each participant using the FVC Week 26 result minus the Baseline FVC result. Posterior median CFB and the 95% highest posterior density (HPD) interval were derived using a Bayesian repeated measures model. The data presented as "Median" refers to the 'posterior median' and "95% confidence interval" to '95% HPD interval'. |
Baseline (Day 1) and Week 26
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Absolute Change From Baseline in Forced Vital Capacity at Weeks 4, 8, 12 and 18
Tidsramme: Baseline (Day 1) and Weeks 4, 8, 12 and 18
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FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. The maximum of triplicate FVC for each participant, at each timepoint was used for calculations. Baseline was defined as the last non-missing value/assessment prior to the first dose of study treatment on Day 1. Change from Baseline was calculated as the value at indicated time point minus the value at Baseline. Posterior median CFB and the 95% HPD interval were derived using a Bayesian repeated measures model. The data presented as "Median" refers to the 'posterior median' and "95% confidence interval" to '95% HPD interval'. |
Baseline (Day 1) and Weeks 4, 8, 12 and 18
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Absolute Change From Baseline in FVC (Percentage [%] Predicted) at Weeks 4, 8, 12, 18 and 26
Tidsramme: Baseline (Day 1) and Weeks 4, 8, 12, 18 and 26
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FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. The maximum of triplicate FVC for each participant, at each timepoint was used for calculations. The FVC (percentage [%] predicted) result at each timepoint for each participant is calculated using the formula: FVC (% predicted) equals to FVC (mL) divided by Predicted FVC (mL) multiply by 100. Baseline was defined as the last non-missing value/assessment prior to the first dose of study treatment on Day 1. Change from Baseline in FVC (% predicted) at each time point for each participant was calculated by subtracting the Baseline FVC (% predicted) from the FVC (% predicted) at that timepoint. |
Baseline (Day 1) and Weeks 4, 8, 12, 18 and 26
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Proportion of Participants Who Achieved Relative Decline of Less Than or Equal to (<=) 5% in FVC From Baseline at Week 26
Tidsramme: Baseline (Day 1) and Week 26
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FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Baseline was defined as the last non-missing value/assessment prior to the first dose of study treatment on Day 1. Relative decline from Baseline in FVC (mL) at the Week 26 visit was calculated using the following formula: relative decline at Week 26 equals to (1 minus Week 26 FVC [mL] divided by Baseline FVC [mL]) multiplied by 100. Participants with relative decline of <=5% at Week 26 were classified as responders; those with greater than (>) 5% decline were non-responders. Participants who died due to disease progression prior to Week 26 were imputed as non-responders. Posterior median and the 95% HPD interval were derived using a Bayesian logistic regression model. The data presented as "Median" refers to the 'posterior median' and "95% confidence interval" to '95% HPD interval'. |
Baseline (Day 1) and Week 26
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Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: Up to Week 29
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or any other situation according to medical or scientific judgment. |
Up to Week 29
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Number of Participants With Vital Signs Results by Potential Clinical Importance (PCI) Criteria
Tidsramme: Up to Week 29
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Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate were measured for at least 5 minutes of rest for the participant in a quiet setting. PCI ranges were SBP (low: less than [<]85 millimeter of mercury [mmHg], high: >180 mmHg), DBP (low: <45 mmHg, high: >110 mmHg) and pulse rate (low: <40 beat per minute [bpm], high: >110 bpm). Participants were counted in the worst-case category if their value changed 'To Low' or 'To High', unless there was no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in 'To Within Range or No Change' category. Participants were counted twice if the participants had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. |
Up to Week 29
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Number of Participants With Electrocardiogram (ECG) Results by PCI Criteria
Tidsramme: Up to Week 29
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Triplicate 12-lead ECGs were obtained after participant has rested in supine position for 5 minutes, using an ECG machine that automatically calculates heart rate and measures PR, QRS, QT, and QTc intervals. ECG parameters with PCI ranges were: PR Interval (low: <110 milliseconds[msec], high: >220 msec), QRS Duration (low: <75 msec, high: >120 msec) and QTcF Interval (<=450 msec, >450 msec to <=480 msec, >480 msec to <=500 msec and >500 msec). Participants were counted in the worst-case category if their value changed 'To Low' or 'To High', unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in 'To Within Range or No Change' category. Participants were counted twice if the participants had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. |
Up to Week 29
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Number of Participants With Hematology Laboratory Results by PCI Criteria
Tidsramme: Up to week 29
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Hematology parameters with PCI ranges were: hematocrit (low: <0.1 percentage of red blood cells in blood, high: >0.54 percentage of red blood cells in blood), lymphocytes (low: <0.8*giga cells per liter [10^9/L]), neutrophil count (low: <1.5*10^9/L), platelet count (low: <100*10^9/L and high: >800*10^9/L), and white blood cell (WBC) (low: <2*10^9/L and high: >25*10^9/L). Participants were counted in the worst-case category if their value changed 'To Low' or 'To High', unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in 'To Within Range or No Change' category. Participants were counted twice if the participants had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. |
Up to week 29
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Number of Participants With Hepatobiliary Laboratory Results by PCI Criteria
Tidsramme: Up to week 29
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Hepatobiliary parameters with PCI ranges were: Alanine transaminase (ALT) (high: greater than or equal to [>=] 3*upper limit of normal [ULN]), Aspartate aminotransferase (AST) (high: >=3*ULN), Alkaline phosphatase (ALP) (high: >=2*ULN) and total bilirubin (high: >=2*ULN). Participants were counted in the worst-case category if their value changed 'To Low' or 'To High', unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in 'To Within Range or No Change' category. Participants were counted twice if the participants had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. |
Up to week 29
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Number of Participants With Clinical Chemistry Laboratory Results by PCI Criteria
Tidsramme: Up to Week 29
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Clinical chemistry parameters with PCI ranges were: glucose (low: <2 millimoles per liter[mmol/L], high: >25 mmol/L), albumin (low: <30 grams per liter[g/L]), creatine phosphokinase (CPK) (high: >1500 international units per liter [IU/L]), potassium (low: <3 mmol/L, high: >6.0 mmol/L), sodium (low: <130 mmol/L, high: >155 mmol/L), blood urea nitrogen (BUN) (high: >14 mmol/L) and calcium corrected for albumin (low: <1.9 mmol/L, high: >3 mmol/L). Participants were counted in the worst-case category if their value changed 'To Low' or 'To High', unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in 'To Within Range or No Change' category. Participants were counted twice if the participants had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. |
Up to Week 29
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Maximum Observed Plasma Concentration (Cmax) of GSK3915393
Tidsramme: Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Blood samples were collected at the indicated nominal time points for pharmacokinetic (PK) analysis of GSK3915393. |
Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 4 Hours (AUC [0-4]) of GSK3915393
Tidsramme: Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Blood samples were collected at the indicated nominal time points for pharmacokinetic analysis of GSK3915393. |
Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to Infinity (AUC [0-inf]) of GSK3915393
Tidsramme: Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Blood samples were collected at the indicated nominal time points for pharmacokinetic analysis of GSK3915393. |
Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Studieleder: GSK Clinical Trials, GlaxoSmithKline
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 220929
- 2023-509371-16-00 (Anden identifikator: EU CT Number)
- 2023 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to gsk-patient-level-data-sharing-july2025.pdf
IPD-delingstidsramme
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
IPD-delingsadgangskriterier
Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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