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GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03457727
Recruitment Status : Completed
First Posted : March 7, 2018
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: Danirixin Drug: Omeprazole Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Subjects will receive danirixin reference and test formulations in a cross-over manner.
Masking: None (Open Label)
Masking Description: This will be an open-label study and blinding will not be performed.
Primary Purpose: Treatment
Official Title: A Two Part, Randomized, Open-label, Cross Over Study in Healthy Elderly Participants to Evaluate the Relative Bioavailability of Hydrobromide Salt Tablet Formulations of Danirixin in the Fed and Fasted States, and to Evaluate the Effect of Food and Gastric Acid Secretion Suppression on Danirixin Pharmacokinetics Following Administration of Hydrobromide Salt Tablets
Actual Study Start Date : March 7, 2018
Actual Primary Completion Date : July 25, 2018
Actual Study Completion Date : July 25, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Subjects receiving danirixin: Part A
Subjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner.
Drug: Danirixin
Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.

Experimental: Subjects receiving danirixin without omeprazole: Part B
Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner.
Drug: Danirixin
Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.

Experimental: Subjects receiving danirixin with omeprazole: Part B
Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner.
Drug: Danirixin
Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.

Drug: Omeprazole
Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.




Primary Outcome Measures :
  1. Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  2. AUC (0-inf) of danirixin 475 milligrams (mg) direct comparison (DC) formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  3. AUC (0-inf) of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  4. AUC (0-inf) of danirixin 600 mg Hydroxypropyl Methylcellulose (HPMC) formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  5. Maximum Observed Concentration (Cmax) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  6. Cmax of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  7. Cmax of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  8. Cmax of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  9. Number of subjects with adverse events (AEs) and serious AEs (SAEs) [ Time Frame: Up to 58 days ]
    An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  10. Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) findings [ Time Frame: Up to 58 days ]
    SBP and DBP will be measured at specific time points in a semi-supine position after at least 5 minutes of rest.

  11. Number of subjects with abnormal pulse rate findings [ Time Frame: Up to 58 days ]
    Pulse rate will be measured at specific time points in a semi-supine position after at least 5 minutes of rest.

  12. Number of subjects with abnormal respiratory rate findings [ Time Frame: Up to 58 days ]
    Respiratory rate will be measured at specific time points in a semi-supine position after at least 5 minutes of rest.

  13. Number of subjects with abnormal body temperature findings [ Time Frame: Up to 58 days ]
    Oral temperature will be measured at specific time points in a semi-supine position after at least 5 minutes of rest.

  14. Number of subjects with abnormal electrocardiogram (ECG) findings [ Time Frame: Up to 58 days ]
    12-lead ECG will be obtained at specific time points using an ECG machine.

  15. Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to 58 days ]
    Laboratory assessment for clinical chemistry parameters will include blood urea nitrogen (BUN), creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, total protein and albumin.

  16. Number of subjects with abnormal clinical hematology parameters [ Time Frame: Up to 58 days ]
    Laboratory assessment for clinical hematology will include platelet, red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), percent reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils

  17. Number of subjects with abnormal urinalysis parameters [ Time Frame: Up to 58 days ]
    Laboratory assessment for urinalysis will include specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite and leukocyte.

  18. AUC from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  19. AUC (0-t) of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  20. AUC (0-t) of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  21. AUC (0-t) of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  22. AUC from time zero (pre-dose) to 24 hours post dose (AUC[0-24]) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  23. AUC (0-24) of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  24. AUC (0-24) of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  25. AUC (0-24) of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  26. Time of occurrence of Cmax (Tmax) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  27. Tmax of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  28. Tmax of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  29. Tmax of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  30. Terminal phase half-life (T1/2) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  31. T1/2 of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  32. T1/2 of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  33. T1/2 of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  34. Time of last quantifiable concentration (Tlast) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  35. Tlast of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  36. Tlast of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  37. Tlast of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  38. Lag time before observation of drug concentrations in sampled matrix (Tlag) of danirixin reference formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin reference formulation.

  39. Tlag of danirixin 475 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 475 mg DC formulation.

  40. Tlag of danirixin 600 mg DC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg DC formulation.

  41. Tlag of danirixin 600 mg HPMC formulation: Part A [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin 600 mg HPMC formulation.

  42. AUC (0-inf) of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  43. AUC (0-t) of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  44. AUC (0-24) of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  45. Cmax of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  46. Tmax of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  47. T1/2 of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  48. Tlast of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  49. Tlag of danirixin formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points for PK analysis of danirixin selected formulation.

  50. AUC (0-inf) of danirixin formulation administered with omeprazole (OMP): Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  51. AUC (0-t) of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  52. AUC (0-24) of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  53. Cmax of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  54. Tmax of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  55. T1/2 of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  56. Tlast of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  57. Tlag of danirixin formulation administered with OMP: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed and fasted state at indicated time-points for PK analysis of danirixin selected formulation.

  58. AUC (0-inf) of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  59. AUC (0-inf) of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  60. AUC (0-t) of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  61. AUC (0-t) of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  62. AUC (0-24) of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  63. AUC (0-24) of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  64. Cmax of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  65. Cmax of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  66. Tmax of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  67. Tmax of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  68. T1/2 of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  69. T1/2 of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  70. Tlast of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  71. Tlast of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  72. Tlag of danirixin reference formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.

  73. Tlag of danirixin mono formulation: Part B [ Time Frame: Pre-dose, 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours post-dose on Day 1 ]
    Blood samples will be collected in the fed state at indicated time-points to assess relative bioavailability of danirixin.



Information from the National Library of Medicine

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


Ages Eligible for Study:   65 Years to 80 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.
  • Subjects who are healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives. Additionally, laboratory assessments that are specifically listed in the inclusion or exclusion criteria and are outside of the reference range can be repeated once during the screening period.
  • Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m^2) (inclusive).
  • Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 60 hours after the last dose of study treatment.
  • Capable of giving signed informed consent.
  • AST, ALT, alkaline phosphatase and bilirubin <= 1.5 × upper limit of normal (ULN) (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
  • Resting BP of <= 160/90 millimeters of mercury (mmHg), irrespective of anti-hypertensive medication status for the subject.
  • Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30 minutes in each of the four treatment periods where study treatment is administered in a fed state.

Exclusion Criteria:

  • Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test [TST; defined as a skin induration <5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history] or a positive (not indeterminate) QuantiFERON®-TB Gold test.
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Breast cancer within the past 10 years.
  • ALT >1.5x ULN
  • Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Corrected QT interval (QTc) >450 milliseconds (msec).
  • Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), 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 treatment until completion of the last study assessment , unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit; Antacids up to 24 hours prior to dosing.
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
  • 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: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Participation in a previous clinical trial with danirixin within 1 year prior to the first dosing day in the current study.
  • Female Subjects: Positive urine beta-human chorionic gonadotropin (beta-hCG) test at screening.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
  • For potent immunosuppressive agents, presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion from the study even if HBsAg is negative.
  • Positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Regular use of known drugs of abuse.
  • Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study treatment until collection of the final blood sample.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 90 days prior to screening.
  • Sensitivity to heparin or heparin-induced thrombocytopenia.
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Information from the National Library of Medicine

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

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03457727


Locations
United States, Kansas
GSK Investigational Site
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03457727     History of Changes
Other Study ID Numbers: 207573
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Danirixin
Healthy
Food effect
Relative Bioavailability
Hydrobromide Salt

Additional relevant MeSH terms:
Omeprazole
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action