Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants

NCT04484337 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 212482
• Study Type: interventional
• Target: 138
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

HIV Infections

Keywords

Cabotegravir; Long-Acting Injection; Pharmacokinetics; Safety; Tolerability

Outcome Measures

Primary Outcomes (15)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Injection 2 - Day 1 to Week 4

Secondary Outcomes (13)

• Part 1 and Part 2: Number of Participants With Adverse Events (AEs) in Injection Phase and Follow up Phase

  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

  From Injection 1 day 1 up to 52 weeks follow-up

• Cmax for CAB Following Oral 30 mg Administration

  Up to Day 29

• Tmax for CAB Following Oral 30 mg Administration

  Up to Day 29

• AUC(0-t) for CAB Following Oral 30 mg Administration

  Up to Day 29

Study Arms (15)

Oral Cabotegravir (CAB) 30

EXPERIMENTAL

Participants received oral dose of CAB 30 milligram (mg) tablet once daily for Days 1 to 28 in the oral lead in phase.

Drug: Cabotegravir sodium (Oral Lead In)

Part 1: Cohort 1 (C1) CAB 400

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL

Part 1: Cohort 1 (C1) CAB200

ACTIVE COMPARATOR

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL

Part 1: Cohort 2 (C2) CAB400

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) subcutaneously in the abdomen, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL

Part 1: Cohort 2 (C2) CAB200

ACTIVE COMPARATOR

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 300 mg and Injection 2: 200 mg respectively) subcutaneously in the abdomen, 4 weeks apart, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL

Part 1: Cohort 3 (C3) CAB400

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL

Part 1: Cohort 3 (C3) CAB200

ACTIVE COMPARATOR

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL

Part 1: Cohort 4 (C4) CAB400

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB400 mg/mL (Injection 1: 400 mg and Injection 2: 200 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL

Part 1: Cohort 4 (C4) CAB200

ACTIVE COMPARATOR

Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 400 mg and Injection 2: 100 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL

Part 1: Cohort 4b Group 1 (C4b G1)

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL; Drug: Topical Non-steroidal anti-inflammatory drug (NSAID); Drug: Topical steroid; Drug: Topical NSAID placebo; Drug: Topical steroid placebo

Part 1: Cohort 4b Group 2 (C4b G2)

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL; Drug: Topical Non-steroidal anti-inflammatory drug (NSAID); Drug: Topical steroid; Drug: Topical NSAID placebo; Drug: Topical steroid placebo

Part 1: Cohort 4h (C4h) CAB400 + rHuPH20

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 400 mg/mL along with 5000 units (U) of recombinant human hyaluronidase PH20 (rHuPH20) sequentially.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Part 1: Cohort 4h (C4h) CAB200 + rHuPH20

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 200 mg/mL along with 5000 U of rHuPH20 sequentially.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL; Drug: Recombinant human hyaluronidase PH20 (rHuPH20)

Part 2: Cohort 5 (C5) CAB400

EXPERIMENTAL

Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 800 mg of CAB 400 mg/mL approximately 12 weeks apart.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL

Part 2: Cohort 5 (C5) CAB200

ACTIVE COMPARATOR

Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 400 mg of CAB 200 mg/mL approximately 12 weeks apart. The dose was matched to the volume of CAB 400 mg/mL administered earlier in the same cohort.

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 200 mg/mL

Interventions

Topical Non-steroidal anti-inflammatory drug (NSAID) DRUG

NSAID applied topically.

Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2)

Cabotegravir sodium (Oral Lead In) DRUG

CAB 30 mg tablets administered orally.

Oral Cabotegravir (CAB) 30; Part 1: Cohort 1 (C1) CAB 400; Part 1: Cohort 1 (C1) CAB200; Part 1: Cohort 2 (C2) CAB200; Part 1: Cohort 2 (C2) CAB400; Part 1: Cohort 3 (C3) CAB200; Part 1: Cohort 3 (C3) CAB400; Part 1: Cohort 4 (C4) CAB200; Part 1: Cohort 4 (C4) CAB400; Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2); Part 1: Cohort 4h (C4h) CAB200 + rHuPH20; Part 1: Cohort 4h (C4h) CAB400 + rHuPH20; Part 2: Cohort 5 (C5) CAB200; Part 2: Cohort 5 (C5) CAB400

Cabotegravir 400 mg/mL DRUG

CAB 400 mg/mL administered intramascularly or subcutaneously.

Part 1: Cohort 1 (C1) CAB 400; Part 1: Cohort 2 (C2) CAB400; Part 1: Cohort 3 (C3) CAB400; Part 1: Cohort 4 (C4) CAB400; Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2); Part 1: Cohort 4h (C4h) CAB400 + rHuPH20; Part 2: Cohort 5 (C5) CAB400

Cabotegravir 200 mg/mL DRUG

CAB 200 mg/mL administered intramascularly or subcutaneously.

Part 1: Cohort 1 (C1) CAB200; Part 1: Cohort 2 (C2) CAB200; Part 1: Cohort 3 (C3) CAB200; Part 1: Cohort 4 (C4) CAB200; Part 1: Cohort 4h (C4h) CAB200 + rHuPH20; Part 2: Cohort 5 (C5) CAB200

Topical steroid DRUG

Steroid medication applied topically.

Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2)

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

rHuPH20 administered subcutaneously.

Part 1: Cohort 4h (C4h) CAB200 + rHuPH20; Part 1: Cohort 4h (C4h) CAB400 + rHuPH20

Topical NSAID placebo DRUG

Placebo for NSAID applied topically.

Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2)

Topical steroid placebo DRUG

Placebo for steroid applied topically.

Part 1: Cohort 4b Group 1 (C4b G1); Part 1: Cohort 4b Group 2 (C4b G2)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by medical evaluation.

You may not qualify if:

• Participants who are negative on two consecutive tests for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), performed at Screening and within 5 days of admission to the Phase I unit, using an approved molecular test (Polymerase chain reaction \[PCR\]).
• Body weight more than or equal to (\>=)40 kilogram (kg) and body mass index (BMI) within the range 18 to 32 kilogram per square meter (kg/m\^2).
• Male participants are eligible to participate if they agree to use contraceptive methods and refrain from donating sperm.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (\<)1 percent(%).
• Capable of giving signed informed consent.
• Signs and symptoms which in the opinion of the investigator are suggestive of Coronavirus disease 2019 (COVID-19) (that is \[i.e.\] fever, cough etc) within 14 days of inpatient admission.
• Contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission.
• History or presence of/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 intervention or interfering with the interpretation of data.
• Abnormal blood pressure as determined by the investigator.
• Alanine transaminase (ALT) more than (\>)1.5 times upper limit of normal (ULN).
• Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Corrected QT interval (QTc) \>450 milliseconds (msec).
• A known hypersensitivity to hyaluronidases (Cohort 4h only).
• The participant has an underlying skin disease or disorder (infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that would interfere with assessment of injection sites.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (5)

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

GSK Investigational Site

Berlin, New Jersey, 08009, United States

Location

GSK Investigational Site

Austin, Texas, 78744, United States

Location

GSK Investigational Site

Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Lead; Anti-Inflammatory Agents, Non-Steroidal; Steroids

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Metals; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind (sponsor-unblind) study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: July 31, 2020
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2023
• Last Updated: May 29, 2026
• Results First Posted: May 29, 2026

Record last verified: 2026-02

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, key secondary endpoints and safety data 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

US (4); NZ (1)