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 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 (29)

• Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 4

• Cmax for cabotegravir (Part 1 Injection 2)

  Injection 2 Day 1 to Week 52 follow-up

• Cmax for cabotegravir (Part 2 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 12

• Cmax for cabotegravir (Part 2 Injection 2)

  Injection 2 Day 1 to Week 52 follow-up

• Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 4

• Tmax for cabotegravir (Part 1 Injection 2)

  Injection 2 Day 1 to Week 52 follow-up

• Tmax for cabotegravir (Part 2 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 12

• Tmax for cabotegravir (Part 2 Injection 2)

  Injection 2 Day 1 to Week 52 follow-up

• Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 4

• AUC(0-t) for cabotegravir (Part 1 Injection 2)

  Injection 2 Day 1 to Injection 2 Week 4

• AUC(0-t) for cabotegravir (Part 2 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 12

• AUC(0-t) for cabotegravir (Part 2 Injection 2)

  Injection 2 Day 1 to Injection 2 Week 12

• Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 4

• Ctau for cabotegravir (Part 1 Injection 2)

  Injection 2 Day 1 to Injection 2 Week 4

• Ctau for cabotegravir (Part 2 Injection 1)

  Injection 1 Day 1 to Injection 1 Week 12

• Ctau for cabotegravir (Part 2 Injection 2)

  Injection 2 Day 1 to Injection 2 Week 12

• Apparent terminal phase half-life (T1/2) for cabotegravir (Part 1 Injection 2)

  Injection 2 Week 4 to Week 52 follow-up

• T1/2 for cabotegravir (Part 2 Injection 2)

  Injection 2 Week 12 to Week 52 follow-up

• Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2)

  Injection 2 Week 4 to Week 52 follow-up

• KALA for cabotegravir (Part 2 Injection 2)

  Injection 2 Week 12 to Week 52 follow-up

• Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b & 4h at Week4 (Part 1 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)

  At Injection 1 Week 4

• Geometric mean ratio of plasma Ctau of CAB for Cohorts 1,2,3,4, 4b at Week 4 (Part 1 Injection 2) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 12 Ctau following first injection at Week 8 in ATLAS [201585]/FLAIR [201584]Study)

  At Injection 2 Week 4

• Geometric mean ratio of plasma Ctau of CAB for Cohorts 5 and 6 at Week 12(Part 2 Injection 1) compared to historical data of CAB 200 mg/mL IM (gluteus medius) (Week 8 Ctau following first injection at Week 4 in ATLAS [201585]/FLAIR [201584]Study)

  At Injection 1 Week 12

• Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h

  At Injection 1 Week 4

• Geometric mean ratio of plasma trough concentration (Ctau) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b

  At Injection 2 Week 4

• Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h

  At Injection 1 Week 4

• Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b

  At Injection 2 Week 4

• Geometric mean ratio of Plasma Cmax of cabotegravir at Week 4 (Part 1 Injection 1) for each pairwise comparison between Cohorts 1, 2, 3, 4, 4b and 4h

  At Injection 1 Week 4

• Geometric mean ratio of Plasma AUC(0-t) of cabotegravir at Week 4 (Part 1 Injection 2) for each pairwise comparison between Cohorts 1, 2, 3, 4 and 4b

  At Injection 2 Week 4

Secondary Outcomes (13)

• Parts 1 and 2: Number of participants with adverse events (AEs)

  Up to 52 weeks follow-up

• Number of participants with liver biochemistry abnormalities

  Up to 52 weeks follow-up

• Cmax for cabotegravir following oral 30 mg administration

  Up to Day 29

• Tmax for cabotegravir following oral 30 mg administration

  Up to Day 29

• AUC(0-t) for cabotegravir following oral 30 mg administration

  Up to Day 29

Study Arms (15)

Part 1:Cohort 1: CAB 400 mg/mL IM gluteal

EXPERIMENTAL

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

Part 1:Cohort 1: CAB 200 mg/mL IM gluteal

ACTIVE COMPARATOR

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

Part 1:Cohort 2: CAB 400 mg/mL SC abdominal

EXPERIMENTAL

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

Part 1:Cohort 2: CAB 200 mg/mL SC abdominal

ACTIVE COMPARATOR

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

Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh)

EXPERIMENTAL

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

Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh)

ACTIVE COMPARATOR

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

Part 1: Cohort 4: CAB 400 mg/mL (IM or SC)

EXPERIMENTAL

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

Part 1: Cohort 4: CAB 200 mg/mL (IM or SC)

ACTIVE COMPARATOR

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

Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius)

EXPERIMENTAL

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

Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius)

ACTIVE COMPARATOR

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

Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)

EXPERIMENTAL

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

Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)

ACTIVE COMPARATOR

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

Part 1: Cohort 4b: CAB 400 mg/mL (SC)

EXPERIMENTAL

Drug: Cabotegravir sodium (Oral Lead In); Drug: Cabotegravir 400 mg/mL; Drug: Topical non-steroidal anti-inflammatory drug; Drug: Topical steroid; Drug: Placebo creams/gels

Part 1: Cohort 4h: CAB 400 mg/mL (SC)

EXPERIMENTAL

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

Part 1: Cohort 4h: CAB 200 mg/mL (SC)

ACTIVE COMPARATOR

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

Interventions

Cabotegravir sodium (Oral Lead In) DRUG

CAB will be available as 30 mg tablets for oral administration.

Part 1: Cohort 4: CAB 200 mg/mL (IM or SC); Part 1: Cohort 4: CAB 400 mg/mL (IM or SC); Part 1: Cohort 4b: CAB 400 mg/mL (SC); Part 1: Cohort 4h: CAB 200 mg/mL (SC); Part 1: Cohort 4h: CAB 400 mg/mL (SC); Part 1:Cohort 1: CAB 200 mg/mL IM gluteal; Part 1:Cohort 1: CAB 400 mg/mL IM gluteal; Part 1:Cohort 2: CAB 200 mg/mL SC abdominal; Part 1:Cohort 2: CAB 400 mg/mL SC abdominal; Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh); Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh); Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius); Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius); Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius); Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)

Cabotegravir 400 mg/mL DRUG

CAB 400 mg/mL will be available for administration by IM injection or SC Injection.

Part 1: Cohort 4: CAB 400 mg/mL (IM or SC); Part 1: Cohort 4b: CAB 400 mg/mL (SC); Part 1: Cohort 4h: CAB 400 mg/mL (SC); Part 1:Cohort 1: CAB 400 mg/mL IM gluteal; Part 1:Cohort 2: CAB 400 mg/mL SC abdominal; Part 1:Cohort 3: CAB 400 mg/mL IM (lateral thigh); Part 2: Cohort 5: CAB 400 mg/mL IM (gluteus medius); Part 2: Cohort 6: CAB 400 mg/mL IM (gluteus medius)

Cabotegravir 200 mg/mL DRUG

CAB 200 mg/mL will be available for administration by IM injection or SC Injection.

Part 1: Cohort 4: CAB 200 mg/mL (IM or SC); Part 1: Cohort 4h: CAB 200 mg/mL (SC); Part 1:Cohort 1: CAB 200 mg/mL IM gluteal; Part 1:Cohort 2: CAB 200 mg/mL SC abdominal; Part 1:Cohort 3: CAB 200 mg/mL IM (lateral thigh); Part 2: Cohort 5: CAB 200 mg/mL IM (gluteus medius); Part 2: Cohort 6: CAB 200 mg/mL IM (gluteus medius)

Topical non-steroidal anti-inflammatory drug DRUG

Non-steroidal anti-inflammatory drug will be available for topical application

Part 1: Cohort 4b: CAB 400 mg/mL (SC)

Topical steroid DRUG

Steroid will be available for topical application

Part 1: Cohort 4b: CAB 400 mg/mL (SC)

Placebo creams/gels DRUG

Placebo creams/gels will be available for topical application

Part 1: Cohort 4b: CAB 400 mg/mL (SC)

Recombinant human hyaluronidase PH20 (rHuPH20) DRUG

rHuPH20 will be available for administration by SC Injection

Part 1: Cohort 4h: CAB 200 mg/mL (SC); Part 1: Cohort 4h: CAB 400 mg/mL (SC)

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

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

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

Model Details: Participants will receive repeat doses of long-acting CAB 400 mg/mL or CAB 200 mg/mL at four-weekly (Q4W) interval in Part 1 and at 12-weekly (Q12W) interval in Part 2.

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: December 4, 2023

Record last verified: 2023-11

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)