This is an active control, randomized study to investigate the safety, tolerability and PK of repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM) (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy adult participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
138
CAB 30 mg tablets administered orally.
CAB 400 mg/mL administered intramascularly or subcutaneously.
CAB 200 mg/mL administered intramascularly or subcutaneously.
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Las Vegas, Nevada, United States
GSK Investigational Site
Berlin, New Jersey, United States
GSK Investigational Site
Austin, Texas, United States
Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h
Blood samples were collected for Pharmacokinetic (PK) analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 1 - Day 1 to Week 4
Part 1 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Day 1 to Week 52 follow-up
Part 2 Injection 1: Tmax for CAB 400 mg/ml Formulation for Cohort 5
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 1 - Day 1 to Week 12
Part 2 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohort 5
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Day 1 to Week 52 follow-up
Part 1 Injection 2: Apparent Terminal Phase Half-life (T1/2) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
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NSAID applied topically.
Steroid medication applied topically.
Placebo for NSAID applied topically.
rHuPH20 administered subcutaneously.
Placebo for steroid applied topically.
GSK Investigational Site
Auckland, New Zealand
Time frame: Injection 2 - Week 4 to Week 52 follow-up
Part 2 Injection 2: T1/2 for CAB 400 mg/ml Formulation for Cohort 5
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Week 12 to Week 52 follow-up
Part 1 Injection 2: Terminal Absorption Elimination Rate Constant (KALA) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Week 4 to Week 52 follow-up
Part 2 Injection 2: KALA for CAB 400 mg/ml Formulation for Cohort 5
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Week 12 to Week 52 follow-up
Part 1 Injection 1: Plasma Trough Concentrations (Ctau) of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Time frame: Injection 1 - Day 1 to Week 4
Part 1 Injection 2: Ctau of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Time frame: Injection 2 - Day 1 to Week 4
Part 2 Injection 1: Ctau of CAB 400 mg/ml Formulation for Cohort 5
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. Ctau is the trough concentration at the end of the dosing interval. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 800mg was presented. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR and ECLAIRE studies.
Time frame: Injection 1 - Day 1 to Week 12
Part 1 Injection 1: Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Time Point (AUC(0-t)) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 1 - Day 1 to Week 4
Part 1 Injection 2: AUC(0-t) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4 and 4b
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Day 1 to Week 4
Part 1 Injection 1: Maximum Observed Plasma Concentration (Cmax) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 1 - Day 1 to Week 4
Part 1 Injection 2: Cmax of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Time frame: Injection 2 - Day 1 to Week 4
Part 1 and Part 2: Number of Participants With Adverse Events (AEs) in Injection Phase and Follow up Phase
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The objective of this analysis is to present the data for participants that received at least an intramuscular or subcutaneous study injection of CAB 400 mg/mL or CAB 200 mg/mL with rHuPH20 formulation.
Time frame: From Injection 1 day 1 up to 52 weeks follow-up
Part 1 and Part 2: Number of Participants With Liver Biochemistry Abnormalities in Injection Phase and Follow up Phase
Blood samples were collected at indicated timepoints to analyze the liver biochemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), Bilirubin and Direct Bilirubin. The objective of this analysis is to present the data for participants that received at least an intramuscular or subcutaneous study injection of CAB 400 mg/mL or CAB 200 mg/mL with rHuPH20 formulation.
Time frame: From Injection 1 day 1 up to 52 weeks follow-up
Cmax for CAB Following Oral 30 mg Administration
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods.
Time frame: Up to Day 29
Tmax for CAB Following Oral 30 mg Administration
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods.
Time frame: Up to Day 29
AUC(0-t) for CAB Following Oral 30 mg Administration
Blood samples were collected for PK analysis of CAB after subcutaneous administration. The PK parameters were calculated by non-compartmental analysis.
Time frame: Up to Day 29
Concentration at 24 Hours (C24) for CAB Following Oral 30 mg Administration
Time frame: At 24 hours
Ctau for CAB Following Oral 30 mg Administration
Time frame: Up to 24 hours on day 29 (Oral lead in phase)
Cmax of CAB 200 for Cohort 4h
Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameter was determined using standard non-compartmental methods.
Time frame: Injection 1 - Day 1 to Week 52 follow-up
Tmax of CAB 200 for Cohort 4h
Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameter was determined using standard non-compartmental methods.
Time frame: Injection 1 - Day 1 to Week 52 follow-up
AUC(0-t) of CAB 200 for Cohort 4h
Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameters were determined using standard non-compartmental methods.
Time frame: Injection 1 - Day 1 to Week 52 follow-up
Ctau of CAB 200 for Cohort 4h and in ATLAS/FLAIR Study
Blood samples were collected for PK analysis of CAB after subcutaneous administration. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 400mg was presented.
Time frame: Injection 1 - Day 1 to Week 52 follow-up
T1/2 of CAB 200 & CAB 400 for Cohort 4h
Blood samples were collected for PK analysis of CAB after subcutaneous administration. The PK parameters were calculated by non-compartmental analysis.
Time frame: Injection 1 - Day 1 to Week 52 follow-up
KALA of CAB 200 & CAB 400 for Cohort 4h
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected for PK analysis of CAB after subcutaneous administration. PK parameters were determined using standard non-compartmental methods.
Time frame: Injection 1 - Day 1 to Week 52 follow-up