A Safety, Tolerability, Acceptability, and Pharmacokineti... | NCT03422172

Status Module

Name	Class
PPD Development, LP	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
Subjects receiving CAB	Experimental	Eligible subjects will receive oral doses of CAB 30 milligrams (mg) tablets once daily for 4 weeks followed by IM injectable suspension of CAB LA 600 mg at Week 5, Week 9, Week 17, Week 25 and Week 33. There will be an approximately 1-week washout period between the last oral dose and the first injection of CAB at Week 5.	Drug: Oral CAB Drug: CAB LA

Name	Type	Description	Arm Group Labels	Other Names
Oral CAB	Drug	CAB tablet will be formulated as white to almost white, oval shaped, film coated 30 mg tablets, administered orally once daily. The CAB tablets will be packaged in bottles containing 30 tablets each.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs): Injection Phase	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or other situations as per investigator's judgement.	Week 5 to 41
Number of Participants With Maximum Toxicity Post-Baseline in Hematology Parameters-Injection Phase	Hematology parameters were graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical hematology parameters included: Activated partial thromboplastin time (APTT) prolonged, hemoglobin (Hb) (increased), white blood cells (WBC) (decreased), lymphocytes count (decreased), neutrophils (decreased), platelets (decreased), prothrombin international normalized ratio (Pro.INR) (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.	Week 5 to 41
Number of Participants With Maximum Toxicity Post-Baseline in Chemistry Parameters: Injection Phase	Chemistry parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical chemistry laboratory parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), bilirubin, calcium (hypercalcemia and hypocalcemia), carbon dioxide (CO2) (decreased), cholesterol (high), Creatine phosphokinase (CPK) increased, Creatinine increased, creatinine clearance (decreased), glucose (hyperglycemia and hypoglycemia), Hypophosphatemia, Potassium (Hyperkalemia and hypokalemia), Sodium (hypernatremia and hyponatremia), Hypertriglyceridemia, uric acid (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Secondary Outcomes

Measure	Description	Time Frame
Ctau Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases	Blood samples were collected at the indicated time points for the determination of Ctau following IM dose of CAB LA and was calculated by standard non-compartmental analysis.	Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

Other Outcomes

Measure	Description	Time Frame
Relationship Between Safety and Tolerability Parameters With Cabotegravir PK Parameters	Relationship between safety and tolerability parameters with cabotegravir PK parameters was planned to be analyzed.	Up to Week 41

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Subjects are male at birth.
Subjects who have non-reactive point of care (POC) HIV test and undetectable HIV-1 ribose nucleic acid (RNA) at screening.
At risk of acquiring HIV, defined as having at least one casual male or female sex partner in the past 24 months.
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring at the time of screening.
Capable of giving written informed consent.
Agree to appropriate use of contraceptive measures during heterosexual intercourse. All subjects should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (example given (e.g.), male condom) to reduce the risk of sexually transmitted infections.
Willing to undergo all required study procedures.

Exclusion Criteria:

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 the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia.
Active skin disease or disorder (that is [i.e.], infection, inflammation, dermatitis, eczema, drug rash, psoriasis, urticaria). Mild cases of localized acne or folliculitis or other mild skin condition may not be exclusionary at the discretion of the Investigator of Record or Medical Monitor.
Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrolment 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 enrolment.
Any medical condition, including psychiatric conditions that in the judgment of the investigator would interfere with the subject's ability to complete study procedures.
Subjects who, in the investigator's judgment, poses a significant suicide risk.
Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis [PEP] or PrEP) in the past 30 days.
Use of high dose aspirin or any other anticoagulant or antiplatelet medication that would interfere with the ability to receive IM injections.
Assessed by the Investigator of Record or designee as being at "high risk" for HIV infection. This may include one or more of the following: the negative partner in an HIV serodiscordant couple where the HIV infected partner is not suppressed; men who exchange sex for goods or money; men who have engaged in any condomless anal intercourse within the past 6 months; men who have had greater than 5 male or female sexual partners within the past 6 months; men who have had a sexually transmitted disease within the past 6 months; any other behavior assessed by the investigator as "high risk".
History of drug or alcohol consumption that in the opinion of the Principal Investigator will interfere with study participation.
Ongoing intravenous drug use - episodic use or any use in the past 90 days is exclusionary (as assessed by the study investigator).
One or more reactive HIV test results at screening or enrolment, even if HIV infection is not confirmed. Negative HIV RNA must also be documented at screening.
Co-enrolment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrolment and receipt of the active arm (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation).
Any of the following laboratory values during the screening period: positive hepatitis C antibody result; positive Hepatitis B surface antigen (HBsAg); hemoglobin <11 grams per deciliter (g/dL); absolute neutrophil count <750 cells/ cubic millimeter (mm^3); platelet count <=100,000 cells/mm^3; presence of a coagulopathy as defined by an international normalized ratio(INR)>1.5 or a partial thromboplastin time (PTT) >45 seconds; calculated creatinine clearance <60 milliliter/minute (mL/minute) using the Cockcroft-Gault equation; a single repeat test is allowed during the screening period to verify a result, with the exception of HIV tests.
Subjects with an ALT, alkaline phosphatase or bilirubin >=1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.

Name	Affiliation	Role
GSK Clinical Trials	ViiV Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Hangzhou	Zhejiang	310000	China
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
35129374	Derived	Han K, Wannamaker P, Lu H, Zhu B, Wang M, Paff M, Spreen WR, Ford SL. Safety, Tolerability, Pharmacokinetics, and Acceptability of Oral and Long-Acting Cabotegravir in HIV-Negative Chinese Men. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0205721. doi: 10.1128/AAC.02057-21. Epub 2022 Feb 7.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cabotegravir	Participants received 30 milligrams (mg) Cabotegravir tablet once daily orally for 4 weeks. Participants who completed the oral lead-in phase, received CAB LA 600 mg administered as a single 3 milliliter (mL) intramuscular (IM) injection on Weeks 5, 9, 17, 25 and 33 during injection phase. There was a washout of 7 days between oral and Injection phase. Participants were followed-up till Week 89 (long-term follow-up phase).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 6, 2018	Apr 9, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs): Injection Phase

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or other situations as per investigator's judgement.

Safety Injection Population. It comprised of all participants who received at least one CAB LA injection.

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG00047

Title

Denominators

Categories

Non-serious AEs

Title	Measurements
	OG00047

SAEs

Title	Measurements
	OG0001

Primary

Number of Participants With Maximum Toxicity Post-Baseline in Hematology Parameters-Injection Phase

Hematology parameters were graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical hematology parameters included: Activated partial thromboplastin time (APTT) prolonged, hemoglobin (Hb) (increased), white blood cells (WBC) (decreased), lymphocytes count (decreased), neutrophils (decreased), platelets (decreased), prothrombin international normalized ratio (Pro.INR) (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Safety Injection Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category title).

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants

Primary

Number of Participants With Maximum Toxicity Post-Baseline in Chemistry Parameters: Injection Phase

Chemistry parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical chemistry laboratory parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), bilirubin, calcium (hypercalcemia and hypocalcemia), carbon dioxide (CO2) (decreased), cholesterol (high), Creatine phosphokinase (CPK) increased, Creatinine increased, creatinine clearance (decreased), glucose (hyperglycemia and hypoglycemia), Hypophosphatemia, Potassium (Hyperkalemia and hypokalemia), Sodium (hypernatremia and hyponatremia), Hypertriglyceridemia, uric acid (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Safety Injection Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category title).

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Primary

Number of Participants With Maximum Toxicity Post-Baseline in Urinalysis Parameters: Injection Phase

Urinalysis parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Urinalysis parameters included: Protein. Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Safety Injection Population. Only those participants with data available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

Number of Participants With Shift From Baseline in Vital Signs With Respect to Clinical Concern Range: Injection Phase

Vital signs were measured after participants had rested in supine position for at least 5 minutes. Clinical concern ranges were: systolic blood pressure (SBP) (Low: <85 millimeters of mercury [mmHg], High: >160 mmHg), diastolic blood pressure (DBP) (Low: <45 mmHg, High: >100 mmHg), pulse rate (Low: <40 mmHg, High: >100 mmHg). Worst case results are presented. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.

Safety Injection Population.

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants

Primary

Number of Participants Withdrawn Due to AEs- Injection Phase

Safety Injection Population

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

Number of Participants Experiencing Injection Site Reactions (ISR)-Injection Phase

Injection site reactions were recorded via ISR diaries and managed through investigator assessment. Number of participants who experienced any injection site reaction (like pain, itching, bruising, bump, discoloration, redness, skin firmness, swelling, warm to touch etc.) is presented.

Safety Injection Population

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

Concentration of Cabotegravir in Plasma at the End of the Dosing Interval (Ctau)-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Ctau following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral Pharmacokinetic (PK) Population. It consisted of all participants in the 'Safety Population' for whom an intensive oral PK sample was obtained and analyzed. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Dosing of Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of AUC(0-tau) following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*micrograms per milliliter

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Maximum Observed Concentration (Cmax) Following Oral Dosing With Cabogegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Cmax following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Time of Occurrence of Cmax (Tmax) Following Oral Dosing With Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Tmax following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Apparent Clearance Following Oral Dosing (CL/F) Following Dosing With Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of CL/F following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Terminal Absorption Elimination Half-life (t1/2) Following Oral Dosing With Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of t1/2 following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Apparent Terminal Phase Rate Constant (Lambda z) Following Oral Dosing With Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Lambda z following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Per hour

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Volume of Distribution at Steady State (Vss) Following Oral Dosing With Cabotegravir-Oral lead-in Phase

Blood samples were collected at the indicated time points for the determination of Vss following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.

Oral PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters

Day 27: Pre-dose and at 1, 2, 3, 4, 8, 24 and 168 hours post-dose

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Primary

Ctau Following IM Dosing With CAB LA During Injection Phase

Blood samples were collected at the indicated time points for the determination of Ctau following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 41) PK Population. It consisted of all participants in the 'Safety Population' for whom an injection PK sample was obtained and analyzed during Weeks 5 to 41. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

AUC(0-tau) Following IM Dosing With CAB LA During Injection Phase

Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 41) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

Cmax Following IM Dosing With CAB LA During Injection Phase

Blood samples were collected at the indicated time points for the determination of Cmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 41) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Primary

Tmax Following IM Dosing With CAB LA During Injection Phase

Blood samples were collected at the indicated time points for the determination of Tmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 41) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hour

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Secondary

Ctau Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of Ctau following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) PK Population. It consisted of all participants in the 'Safety Population' for whom an injection PK sample was obtained and analyzed during Weeks 5 to 89 (through Injection and long-term follow-up phases). Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

AUC(0-tau) Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of AUC(0-tau) following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

Cmax Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of Cmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) (PK) Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Micrograms per milliliter

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

Tmax Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of Tmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hour

Pre-dose sample on Weeks 7 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

CL/F Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of CL/F following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

Pre-dose sample on Weeks 7, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

T1/2 Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of t1/2 following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) PK Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

Lambda z Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of Lambda z following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) (PK) Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Per hour

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

Vss Following IM Dosing With CAB LA Through Injection and Long-term Follow-up Phases

Blood samples were collected at the indicated time points for the determination of Vss following IM dose of CAB LA and was calculated by standard non-compartmental analysis.

Injection (Week 89) (PK) Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters

Pre-dose sample on Weeks 5, 9, 17, 25, 33; Post-dose sample on Weeks 6, 10, 18, 26, 34, 37, 41, 53, 65, 77, 89

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase and Long-term Follow up)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase followed by a long term follow up from Week 41 to 89.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Non-serious AEs and SAEs (Oral lead-in Phase)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity, Is a congenital anomaly/birth defect, other situation as per investigator's judgement.

Safety Population. It comprised all participants who received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants Withdrawn Due to AEs-oral lead-in Phase

Safety Population.

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Maximum Toxicity Post-Baseline in Chemistry Parameters: Oral lead-in Phase

Chemistry parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical chemistry laboratory parameters included ALT, albumin, ALP, AST, bilirubin, calcium (hypercalcemia and hypocalcemia), CO2 decreased, cholesterol, CPK increased, Creatinine increased, creatinine clearance (decreased), glucose (hyperglycemia and hypoglycemia), Hypophosphatemia, Potassium (Hyperkalemia and hypokalemia), Sodium (hypernatremia and hyponatremia), Hypertriglyceridemia, uric acid (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category title).

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants

Secondary

Number of Participants With Maximum Toxicity Post-Baseline in Hematology Parameters: Oral lead-in Phase

Hematology parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical hematology parameters included: APTT prolonged, Hb (increased), WBC (decreased), lymphocytes count (decreased), neutrophils (decreased), platelets (decreased), prothrombin international normalized ratio (Pro.INR) (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.

Safety Population.

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Abnormal Urinalysis Parameters: Oral lead-in Phase

Safety Population.

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Shift From Baseline in Vital Signs With Respect to Clinical Concern Range: Oral lead-in Phase

Vital signs were measured after participants had rested in supine position for at least 5 minutes. Clinical concern ranges were: SBP (Low <85 mmHg, High: >160 mmHg), DBP (Low: <45 mmHg, High: >100 mmHg), pulse rate (Low: <40 mmHg, High: >100 mmHg). Worst case results are presented. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.

Safety Population.

Posted

Count of Participants

Participants

Up to Week 4

ID	Title	Description
OG000	CAB 30 mg (Oral lead-in Phase)	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Injection Discontinuation-Injection Phase

Percentage of participants with injection discontinuation is presented.

Safety Injection Population

Posted

Number

Percentage of participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG00047

Secondary

Number of Participants With Grade 2 to 4 Injection Site Pain-Injection Phase

Severity of injection site reactions was analyzed using DAIDS AE Grading Table. The severity is categorized into grades as following: Grade 1 (mild): causing no or minimal interference with usual social and functional activities, Grade 2 (moderate): causing greater than minimal interference with usual social and functional activities, Grade 3 (severe): causing inability to perform usual social and functional activities, Grade 4 (Potentially life threatening): causing inability to perform basic self-care functions or hospitalization indicated. Higher grade indicates more severe condition. Number of participants who had at least one Grade 2 to 4 Injection site reaction is presented.

Safety Injection Population.

Posted

Count of Participants

Participants

Week 5 to 41

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Secondary

HIV-Prevention Treatment Satisfaction Total Score-Injection Phase

HIV-Prevention Treatment Satisfaction Questionnaire (change) (HIV-PrevTSQc) was used to assess participant tolerability and satisfaction to the treatment. It consisted total 13 questions. The experience of HIV prevention treatment was assessed using a scale from 3 (much more satisfied/effective/convenient/ flexible/likely to recommend the treatment/likely to speak well of the treatment/easier now) to -3 (much less satisfied/effective/convenient/flexible/likely to recommend the treatment/likely to speak well of the treatment/easier now). Total score was calculated by taking sum of scores of all questions. It ranges from -39 to 39, with higher scores indicating more satisfaction.

Safety Injection Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Scores on scale

At Week 10

ID	Title	Description
OG000	CAB LA 600 mg (Injection Phase)	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Acceptability of Cabotegravir for HIV Prevention

Number of participants who consider using cabotegravir for HIV prevention in the future is presented. Participants were asked if they would consider using cabotegravir for HIV prevention in the future and their answers to this question were recorded as 'Yes', 'No' or 'Missing'.

Safety Population.

Posted

Count of Participants

Participants

Up to Week 41

ID	Title	Description
OG000	Cabotegravir	Participants received 30 milligrams (mg) Cabotegravir tablet once daily orally for 4 weeks. Participants who completed the oral lead-in phase, received CAB LA 600 mg administered as a single 3 milliliter (mL) intramuscular (IM) injection on Weeks 5, 9, 17, 25 and 33 during injection phase. There was a washout of 7 days between oral and Injection phase. Participants were followed-up till Week 89 (long-term follow-up phase).

Units	Counts
Participants	OG000

Other Pre-specified

Relationship Between Safety and Tolerability Parameters With Cabotegravir PK Parameters

Relationship between safety and tolerability parameters with cabotegravir PK parameters was planned to be analyzed.

Safety Population. This was a conditional secondary endpoint for which results are not available because population pharmacokinetic (Pop PK) analyses were not conducted.

Posted

Up to Week 41

ID	Title	Description
OG000	Cabotegravir	Participants received 30 milligrams (mg) Cabotegravir tablet once daily orally for 4 weeks. Participants who completed the oral lead-in phase, received CAB LA 600 mg administered as a single 3 milliliter (mL) intramuscular (IM) injection on Weeks 5, 9, 17, 25 and 33 during injection phase. There was a washout of 7 days between oral and Injection phase. Participants were followed-up till Week 89 (long-term follow-up phase).

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mouth ulceration	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected48 at risk EG0012 affected47 at risk EG0020 affected47 at risk
Injection site induration	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0014 affected47 at risk EG0020 affected47 at risk
Injection site pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG00147 affected47 at risk EG0020 affected47 at risk
Injection site pruritus	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected47 at risk EG0020 affected47 at risk
Injection site swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG00122 affected47 at risk EG0020 affected47 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0019 affected47 at risk EG0022 affected47 at risk
Gastroenteritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0011 affected47 at risk EG0023 affected47 at risk
Tonsillitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected47 at risk EG0021 affected47 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0004 affected48 at risk EG00115 affected47 at risk EG0029 affected47 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected47 at risk EG0021 affected47 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected47 at risk EG0022 affected47 at risk
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0014 affected47 at risk EG0020 affected47 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected48 at risk EG0014 affected47 at risk EG0020 affected47 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0013 affected47 at risk EG0020 affected47 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected48 at risk EG0011 affected47 at risk EG0021 affected47 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0012 affected47 at risk EG0022 affected47 at risk
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0012 affected47 at risk EG0024 affected47 at risk
Blood uric acid increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected48 at risk EG0014 affected47 at risk EG0022 affected47 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected48 at risk EG0011 affected47 at risk EG0020 affected47 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected48 at risk EG0012 affected47 at risk EG0021 affected47 at risk

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases
D012897	Slow Virus Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CAB 30 mg - Oral lead-in Phase	Participants received 30 mg Cabotegravir tablet once daily orally for 4 weeks during oral lead-in phase.	48	0	48	13	48
EG001	CAB LA 600 mg - Injection Phase	Participants received CAB LA 600 mg administered as a single 3 mL intramuscular injection on Weeks 5, 9, 17, 25 and 33 during Injection phase.	47	1	47	47	47
EG002	CAB LA 600 mg - Long-term Follow-up Phase	After Injection phase, participants were followed-up till Week 89 (long-term follow-up phase).	47	0	47	17	47

ID	Term
D015658	HIV Infections
D000163	Acquired Immunodeficiency Syndrome