Pharmacokinetic Study of Cabotegravir and Rilpivirine Long-acting Intramuscular Injections in Healthy Adult Participants

NCT04371380 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 208832
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open label study in healthy participants to assess the pharmacokinetics of cabotegravir and rilpivirine in plasma following the administration of a single 600 milligram (mg) and a 900 mg intramuscular (IM) injection respectively, to separate vastus lateralis muscles on each leg. Cabotegravir is an integrase inhibitor being developed in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor, for the treatment of human immunodeficiency virus (HIV). The objective is to evaluate pharmacokinetics, tolerability, and safety of cabotegravir long acting plus rilpivirine long acting administered concomitantly as two separate IM injections in the vastus lateralis muscle of adult healthy participants. The screening phase will be of 30 days, oral lead-in (OLI) phase of 28 days, there will be washout period of 10-14 days, followed by an injection phase and follow-up period will be up to 52-weeks. Approximately 15 adult healthy participants will be enrolled.

Conditions

HIV Infections

Keywords

cabotegravir; rilpivirine; HIV; Pharmacokinetics; intramuscular injection

Outcome Measures

Primary Outcomes (12)

• Maximum Observed Concentration (Cmax) of Cabotegravir (CAB) Following Single IM Injection

  Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Cmax of Rilpivirine (RPV) Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Time of Cmax (Tmax) of CAB Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Tmax of RPV Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time (AUC[0-t]) of CAB Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• AUC(0-t) of RPV Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) of CAB Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• AUC(0-infinity) of RPV Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Apparent Terminal Phase Half-life (t1/2) of CAB Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• t1/2 of RPV Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Geometric Mean of Absorption Rate Constant (KALA) of CAB Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of CAB.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

• Geometric Mean of Absorption Rate Constant (KALA) of RPV Following Single IM Injection

  Blood samples were collected at indicated time points for PK analysis of RPV.

  Day 1 (pre-dose, 1 hour, 2 hours) and one post-dose sample on day 2, day 4, day 5, day 8, day 10, day 15, day 17, day 22, day 28, week 8, week 12, week 24, week 36 and week 52

Secondary Outcomes (2)

• Number of Participants With Liver Related Adverse Events (AEs)

  Up to 56 weeks

• Number of Participants With Liver Related Abnormalities

  Up to 56 weeks

Study Arms (1)

OLI phase followed by Injection phase

EXPERIMENTAL

Participants will be administered cabotegravir at a dose of 30 mg plus rilpivirine dose of 25 mg once daily with meal on Day 1 to Day 28 in OLI phase. There will be 10 to 14 days wash out period after OLI. This will be followed by an injection phase, wherein participants will receive 600 mg cabotegravir long acting given as one 3 milliliter (mL) IM injection plus 900 mg rilpivirine long acting given as one 3 mL IM injection on Day 1.

Drug: Cabotegravir Tablets; Drug: Rilpivirine Tablets; Drug: Cabotegravir extended release suspension for injection (long-acting); Drug: Rilpivirine extended release suspension for injection (long-acting)

Interventions

Cabotegravir Tablets DRUG

Cabotegravir tablets will be white to almost white oval shaped film coated tablets with a unit dose of 30 mg and will be administered orally.

OLI phase followed by Injection phase

Rilpivirine Tablets DRUG

Rilpivirine tablets will be off-white, round, biconvex film coated tablets with a unit dose of 25 mg and will be administered orally.

OLI phase followed by Injection phase

Cabotegravir extended release suspension for injection (long-acting) DRUG

Cabotegravir long-acting will be a sterile white to slightly pink suspension containing 200 mg per mL of GSK1265744 as free acid for administration by intramuscular injection.

OLI phase followed by Injection phase

Rilpivirine extended release suspension for injection (long-acting) DRUG

Rilpivirine long-acting will be a sterile white suspension containing 300 mg per mL of rilpivirine as the free base for administration by intramuscular injection.

OLI phase followed by Injection phase

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 including medical history, physical examination, laboratory tests, and cardiac monitoring.

You may not qualify if:

• Participants who are negative on two consecutive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), performed at Screening and on Day -1 of admission to the Phase I unit, using an approved molecular test (polymerase chain reaction or antigen test).
• Body weight \>=40 kilogram (Kg) and body mass index (BMI) within the range 18 to 35 kg per square meter (inclusive).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form.
• Signs and symptoms which in the opinion of the investigator are suggestive of COVID-19 (example; 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, neurological or psychiatric 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) greater than 1.5 times upper limit of normal (ULN).
• Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• History of ongoing or clinically relevant seizure disorder within the previous 2 years, including participants who have required treatment for seizures within this time period. A prior history of seizure, with a seizure free period of at least 2 years, off anti-epileptics, may be considered for enrollment if the investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the medical monitor prior to enrollment.
• QT interval corrected for heart rate (QTc) greater than 450 millisecond for male participants and greater than 470 milliseconds for female participants
• A participant, who has an underlying skin disease or disorder (i.e. infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria).
• A participant, who is considered to have insufficient musculature to allow safe administration of cabotegravir or rilpivirine in the opinion of the investigator will be excluded.
• Unable to refrain from the use of prescription or non-prescription drugs, including 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 medication to the completion of the follow-up visit unless in the opinion of the Investigator and ViiV medical monitor the medication will not interfere with the study procedures or compromise participant safety.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Janssen Pharmaceuticals: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Rilpivirine; Injections

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)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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: NA
• Masking: NONE
• Masking Details: This is an open label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Eligible participants will receive orally, tablets of cabotegravir plus rilpivirine for 28 days. There will be 10 to 14 days wash out period followed by an IM injection of cabotegravir long-acting plus rilpivirine long-acting.

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 1, 2020
• Study Start: September 16, 2020
• Primary Completion: December 26, 2021
• Study Completion: December 26, 2021
• Last Updated: April 22, 2024
• Results First Posted: April 22, 2024

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 (1)