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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04484337




Registration number
NCT04484337
Ethics application status
Date submitted
20/07/2020
Date registered
23/07/2020

Titles & IDs
Public title
Study to Evaluate Pharmacokinetic (PK), Safety and Tolerability of Cabotegravir (CAB) 400 Milligrams Per Milliliter (mg/mL) Formulation in Healthy Adult Participants
Scientific title
A Phase 1, Two-part, Double-blind, Active-control, Randomized Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat-Dose Cabotegravir (CAB 400 mg/mL Formulation) Long-Acting Injection Following Subcutaneous or Intramuscular Administration in Healthy Adult Participants
Secondary ID [1] 0 0
212482
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabotegravir sodium (Oral Lead In)
Treatment: Drugs - Cabotegravir 400 mg/mL
Treatment: Drugs - Cabotegravir 200 mg/mL
Treatment: Drugs - Topical non-steroidal anti-inflammatory drug
Treatment: Drugs - Topical steroid
Treatment: Drugs - Placebo creams/gels
Treatment: Drugs - Recombinant human hyaluronidase PH20 (rHuPH20)

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

Active comparator: Part 1:Cohort 1: CAB 200 mg/mL IM gluteal -

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

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

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

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

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

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

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

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

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

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

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

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

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


Treatment: Drugs: Cabotegravir sodium (Oral Lead In)
CAB will be available as 30 mg tablets for oral administration.

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

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

Treatment: Drugs: Topical non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug will be available for topical application

Treatment: Drugs: Topical steroid
Steroid will be available for topical application

Treatment: Drugs: Placebo creams/gels
Placebo creams/gels will be available for topical application

Treatment: Drugs: Recombinant human hyaluronidase PH20 (rHuPH20)
rHuPH20 will be available for administration by SC Injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum observed Plasma concentration (Cmax) for cabotegravir (Part 1 Injection 1)
Timepoint [1] 0 0
Injection 1 Day 1 to Injection 1 Week 4
Primary outcome [2] 0 0
Cmax for cabotegravir (Part 1 Injection 2)
Timepoint [2] 0 0
Injection 2 Day 1 to Week 52 follow-up
Primary outcome [3] 0 0
Cmax for cabotegravir (Part 2 Injection 1)
Timepoint [3] 0 0
Injection 1 Day 1 to Injection 1 Week 12
Primary outcome [4] 0 0
Cmax for cabotegravir (Part 2 Injection 2)
Timepoint [4] 0 0
Injection 2 Day 1 to Week 52 follow-up
Primary outcome [5] 0 0
Time of maximum observed plasma concentration (Tmax) for cabotegravir (Part 1 Injection 1)
Timepoint [5] 0 0
Injection 1 Day 1 to Injection 1 Week 4
Primary outcome [6] 0 0
Tmax for cabotegravir (Part 1 Injection 2)
Timepoint [6] 0 0
Injection 2 Day 1 to Week 52 follow-up
Primary outcome [7] 0 0
Tmax for cabotegravir (Part 2 Injection 1)
Timepoint [7] 0 0
Injection 1 Day 1 to Injection 1 Week 12
Primary outcome [8] 0 0
Tmax for cabotegravir (Part 2 Injection 2)
Timepoint [8] 0 0
Injection 2 Day 1 to Week 52 follow-up
Primary outcome [9] 0 0
Area under the concentration - time curve from time zero to last quantifiable time point (AUC[0-t]) for cabotegravir (Part 1 Injection 1)
Timepoint [9] 0 0
Injection 1 Day 1 to Injection 1 Week 4
Primary outcome [10] 0 0
AUC(0-t) for cabotegravir (Part 1 Injection 2)
Timepoint [10] 0 0
Injection 2 Day 1 to Injection 2 Week 4
Primary outcome [11] 0 0
AUC(0-t) for cabotegravir (Part 2 Injection 1)
Timepoint [11] 0 0
Injection 1 Day 1 to Injection 1 Week 12
Primary outcome [12] 0 0
AUC(0-t) for cabotegravir (Part 2 Injection 2)
Timepoint [12] 0 0
Injection 2 Day 1 to Injection 2 Week 12
Primary outcome [13] 0 0
Trough concentrations (Ctau) for cabotegravir (Part 1 Injection 1)
Timepoint [13] 0 0
Injection 1 Day 1 to Injection 1 Week 4
Primary outcome [14] 0 0
Ctau for cabotegravir (Part 1 Injection 2)
Timepoint [14] 0 0
Injection 2 Day 1 to Injection 2 Week 4
Primary outcome [15] 0 0
Ctau for cabotegravir (Part 2 Injection 1)
Timepoint [15] 0 0
Injection 1 Day 1 to Injection 1 Week 12
Primary outcome [16] 0 0
Ctau for cabotegravir (Part 2 Injection 2)
Timepoint [16] 0 0
Injection 2 Day 1 to Injection 2 Week 12
Primary outcome [17] 0 0
Apparent terminal phase half-life (T1/2) for cabotegravir (Part 1 Injection 2)
Timepoint [17] 0 0
Injection 2 Week 4 to Week 52 follow-up
Primary outcome [18] 0 0
T1/2 for cabotegravir (Part 2 Injection 2)
Timepoint [18] 0 0
Injection 2 Week 12 to Week 52 follow-up
Primary outcome [19] 0 0
Absorption rate constant (KALA) for cabotegravir (Part 1 Injection 2)
Timepoint [19] 0 0
Injection 2 Week 4 to Week 52 follow-up
Primary outcome [20] 0 0
KALA for cabotegravir (Part 2 Injection 2)
Timepoint [20] 0 0
Injection 2 Week 12 to Week 52 follow-up
Primary outcome [21] 0 0
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)
Timepoint [21] 0 0
At Injection 1 Week 4
Primary outcome [22] 0 0
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)
Timepoint [22] 0 0
At Injection 2 Week 4
Primary outcome [23] 0 0
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)
Timepoint [23] 0 0
At Injection 1 Week 12
Primary outcome [24] 0 0
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
Timepoint [24] 0 0
At Injection 1 Week 4
Primary outcome [25] 0 0
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
Timepoint [25] 0 0
At Injection 2 Week 4
Primary outcome [26] 0 0
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
Timepoint [26] 0 0
At Injection 1 Week 4
Primary outcome [27] 0 0
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
Timepoint [27] 0 0
At Injection 2 Week 4
Primary outcome [28] 0 0
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
Timepoint [28] 0 0
At Injection 1 Week 4
Primary outcome [29] 0 0
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
Timepoint [29] 0 0
At Injection 2 Week 4
Secondary outcome [1] 0 0
Parts 1 and 2: Number of participants with adverse events (AEs)
Timepoint [1] 0 0
Up to 52 weeks follow-up
Secondary outcome [2] 0 0
Number of participants with liver biochemistry abnormalities
Timepoint [2] 0 0
Up to 52 weeks follow-up
Secondary outcome [3] 0 0
Cmax for cabotegravir following oral 30 mg administration
Timepoint [3] 0 0
Up to Day 29
Secondary outcome [4] 0 0
Tmax for cabotegravir following oral 30 mg administration
Timepoint [4] 0 0
Up to Day 29
Secondary outcome [5] 0 0
AUC(0-t) for cabotegravir following oral 30 mg administration
Timepoint [5] 0 0
Up to Day 29
Secondary outcome [6] 0 0
Concentration at 24 hours (C24) for cabotegravir following oral 30 mg administration
Timepoint [6] 0 0
At 24 hours
Secondary outcome [7] 0 0
Ctau for cabotegravir at Day 29 following oral 30 mg administration
Timepoint [7] 0 0
Up to Day 29
Secondary outcome [8] 0 0
Cmax of cabotegravir for cohort 4h
Timepoint [8] 0 0
Injection 1 Day 1 to Week 52 follow-up
Secondary outcome [9] 0 0
Tmax of cabotegravir for cohort 4h
Timepoint [9] 0 0
Injection 1 Day 1 to Week 52 follow-up
Secondary outcome [10] 0 0
AUC(0-t) of cabotegravir for cohort 4h
Timepoint [10] 0 0
Injection 1 Day 1 to Week 52 follow-up
Secondary outcome [11] 0 0
Ctau of cabotegravir for cohort 4h
Timepoint [11] 0 0
Injection 1 Day 1 to Week 52 follow-up
Secondary outcome [12] 0 0
T1/2 of cabotegravir for cohort 4h
Timepoint [12] 0 0
Injection 1 Day 1 to Week 52 follow-up
Secondary outcome [13] 0 0
KALA of cabotegravir for cohort 4h
Timepoint [13] 0 0
Injection 1 Day 1 to Week 52 follow-up

Eligibility
Key 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.
* A participant with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included if the investigator determines and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* 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.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* 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.
* Exclusion criteria for screening electrocardiogram (ECG):

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/05/2023
Sample size
Target
Accrual to date
Final
138
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Nevada
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
New Zealand
State/province [5] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ViiV Healthcare
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04484337