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

NCT ID: NCT04484337

Last Updated: 2023-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-31

Study Completion Date

2023-05-05

Brief Summary

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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.

Detailed Description

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Conditions

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HIV Infections

Keywords

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Cabotegravir Long-Acting Injection Pharmacokinetics Safety Tolerability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This will be a double-blind (sponsor-unblind) study.

Study Groups

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

Topical non-steroidal anti-inflammatory drug

Intervention Type DRUG

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

Topical steroid

Intervention Type DRUG

Steroid will be available for topical application

Placebo creams/gels

Intervention Type DRUG

Placebo creams/gels will be available for topical application

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

Group Type EXPERIMENTAL

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 400 mg/mL

Intervention Type DRUG

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

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type DRUG

rHuPH20 will be available for administration by SC Injection

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

Group Type ACTIVE_COMPARATOR

Cabotegravir sodium (Oral Lead In)

Intervention Type DRUG

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

Cabotegravir 200 mg/mL

Intervention Type DRUG

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

Recombinant human hyaluronidase PH20 (rHuPH20)

Intervention Type DRUG

rHuPH20 will be available for administration by SC Injection

Interventions

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Cabotegravir sodium (Oral Lead In)

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

Intervention Type DRUG

Cabotegravir 400 mg/mL

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

Intervention Type DRUG

Cabotegravir 200 mg/mL

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

Intervention Type DRUG

Topical non-steroidal anti-inflammatory drug

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

Intervention Type DRUG

Topical steroid

Steroid will be available for topical application

Intervention Type DRUG

Placebo creams/gels

Placebo creams/gels will be available for topical application

Intervention Type DRUG

Recombinant human hyaluronidase PH20 (rHuPH20)

rHuPH20 will be available for administration by SC Injection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (less than or equal to \[\<=\]325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
* Participants considered to have insufficient musculature to allow safe administration of CAB 400 mg/mL (gluteus medius or vastus lateralis).
* 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.
* History of or on-going high-risk behaviors that may put the participant at increased risk for Human Immunodeficiency Virus (HIV) acquisition in the opinion of the investigator. This includes participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.
* Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
* The participant 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: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
* A positive pre-study drug/alcohol screen.

1. Heart rate: For Males \<45 or \>100 beats per minute (bpm), for females \<50 or \>100 bpm.
2. PR Interval: For males and females \<120 or \>220 msec.
3. QRS duration: For males and females \<70 or \>120 msec.
4. QT duration corrected for heart rate by Fridericia's formula (QTcF) interval: For males and females \>450 msec.
* Evidence of previous myocardial infarction.
* Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular \[AV\] block \[2nd degree or higher\], Wolff-Parkinson-White \[WPW\] syndrome).
* Sinus Pauses \>3 seconds.
* Any significant arrhythmia which, in the opinion of the Investigator or GlaxoSmithKline (GSK)/ViiV Medical monitor, will interfere with the safety for the individual participant.
* Non-sustained or sustained ventricular tachycardia (\>=3 consecutive ventricular ectopic beats).
* Positive HIV antibody/antigen test. Participants will be advised regarding safer sex. In the event a participant acquires HIV during the course of the study they will be required to withdraw from the study and will be referred urgently to an HIV treatment center for further management.
* Regular use of known drugs of abuse.
* Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
* Participants with a history of intolerance to or with contraindications to the use of topical non-steroidal anti-inflammatory drugs (NSAIDs) or topical steroids will be excluded from participation in Cohort 4b.
* Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of \>14 units for males or \>7 units for females.
* Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
* The participant has a tattoo or other dermatological condition overlying the location of injection or a prior history of silicone implants (gluteal) which may interfere with interpretation of injection site reactions or administration of CAB LA.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

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GSK Investigational Site

Orlando, Florida, United States

Site Status

GSK Investigational Site

Las Vegas, Nevada, United States

Site Status

GSK Investigational Site

Berlin, New Jersey, United States

Site Status

GSK Investigational Site

Austin, Texas, United States

Site Status

GSK Investigational Site

Auckland, , New Zealand

Site Status

Countries

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United States New Zealand

Other Identifiers

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212482

Identifier Type: -

Identifier Source: org_study_id