Infection, Human Immunodeficiency Virus
Conditions
Keywords
Pre-Exposure Prophylaxis, HIV integrase, Intramuscular Injection, GSK1265744
Brief summary
This study is a Phase IIa, randomized, multi-site, two-arm, double-blinded study to evaluate the safety, tolerability, and acceptability of GSK1265744 long acting injectable formulation (744 LA) in adult male subjects. To evaluate the safety and tolerability of the injectable agent, 744 LA (800 milligrams (mg) dose administered at three time points at 12 week intervals) through Week 41 in HIV-uninfected men. Eligible participants will be randomized in a 5:1 ratio to receive 744 LA or matching placebo. Participants will receive daily oral 744 (30 mg tablets) or matching placebo for 4 weeks during the Oral Phase of the study, followed by a one week washout period. Following safety lab assessments from the Oral Phase, participants will enter the Injection Phase and receive Intramuscular (IM) injections of 744 LA or placebo at three time points at 12 week intervals. IM injections will consist of 800 mg of 744 or a matching control
Interventions
DRUG744 Tablet
White to almost white oval shaped film coated 30 mg tablets for oral administration
DRUG744 LA Injection
Sterile white to slightly coloured suspension containing 200 mg/mL of 744 as free acid for administration by intramuscular (IM) injection
DRUGPlacebo Tablet
Microcrystalline cellulose, Opadry film-coating, white OY-S-28876
DRUGPlacebo Injection
Sterile saline 0.9% Sodium Chloride Injection
Sponsors
GlaxoSmithKline
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-reactive HIV test at screening or enrollment. * Males 18 to 65 years old at the time of signing the informed consent. * At risk of acquiring HIV, defined as having at least one casual 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. * If participating in sexual activity with a female of child-bearing potential, men must agree to use condoms. Subjects who are sexual partners of females with child bearing potential must also agree to practice an acceptable method of contraception for the duration of the study, such as double barrier (male condom/spermicide, male condom/diaphragm) or female partner use of hormonal contraception, intrauterine device (IUD) or other method with published data showing that the lowest expected failure rate for that is less than 1% per year. All subjects participating in the study must be counseled on safer sexual practices including the use of effective barrier methods to minimize risk of HIV transmission. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Willing to undergo all required study procedures
Exclusion criteria
* One or more reactive HIV test results at screening or enrollment, even if HIV infection is not confirmed. Negative HIV Ribonucleic acid (RNA) must also be documented at screening. * 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 Men who exchange sex for goods or money Men who have engaged in unprotected receptive anal intercourse within the past 6 months Men who have had greater than 3 sexual partners within the past 3 months Men who have had a sexually transmitted disease within the past 6 months Any other behavior assessed by the investigator as high risk * Co-enrollment in any other HIV interventional research study (provided by self-report or other available documentation) or prior enrollment and receipt of the active arm (i.e., NOT a placebo) of a HIV vaccine trial (provided by available documentation). * Use of antiretroviral (ARV) therapy (e.g., for Post exposure prophylaxis (PEP) or Pre exposure prophylaxis (PrEP) in the past 30 days, five half-lives, or twice the duration of the biological effect of the applied treatment (whichever is longer) prior to study enrollment. * 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 drug or alcohol consumption that in the opinion of the Principal Investigator will interfere with study participation. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. * Any of the following laboratory values during the screening period. Positive Hepatitis C antibody result Positive Hepatitis B surface antigen (HBsAg) Hemoglobin less than 11 gram (g)/deci liter (dL) Absolute neutrophil count less than 750 cells/mm\^3 Platelet count less than or equal to 100,000/mm\^3 Presence of a coagulopathy as defined by an INR greater than 1.5 or a PTT greater than 45sec Calculated creatinine clearance less than 70 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 alanine aminotransferase (ALT), alkaline phosphatase (ALP) or bilirubin greater than or equal to1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). * History of the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia. * The subject's systolic blood pressure is outside the range of 90-160mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 45-100 beats per minute (bpm). *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Baseline (Week 5) to Week 41 | Vital signs measurements were performed for SBP and DBP following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41. |
| Number of Participants With Any Grade 2 or Higher Event in the Injection Phase | Up to Week 41 | Clinical adverse event (AE) were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41). |
| Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase | Up to Week 41 | The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, sensory organs, systemic hormonal preparations, excluding sex hormones, blood and blood forming organs, cardiovascular system. The participants who took medication from any of the above class of during the injection phase (Week 5-Week 41) have been presented. |
| Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Up to Week 41 | The severity of laboratory results was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for Number of participants who experienced grade 2 or higher laboratory results in the injection phase (Week 5-Week 14) have been presented. |
| Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Up to Week 41 | Full 12-lead ECGs included heart rate, PR, QRS, QT and QTc intervals. Measurements were taken from the participant following 5 minutes of rest in a semi-supine position. ECGs were performed at Week 5, Week 17, Week 29 and Week 41 in the injection phase (Week 5-Week 41). ECG abnormalities characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS) upto Week 41 have been presented. There were no A-CS findings for ECG in the injection phase. |
| Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Baseline (Week 5) to Week 41 | Vital signs measurements were performed for HR following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41. |
| Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | Up to Week 41 | Common ISR included pain, erythema, nodules and any other ISR with greater or equal to 5 participants. The number of participants who experienced pain events by needle length, swelling events by needle length, bump events by needle length for injection phase by maximum grades have been presented for the injection phase (Week 5-Week 41). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Up to Week 4 | Clinical AE were graded using the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41). |
| Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase | Up to Week 41 | Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for AUC(0-tau) a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (i.e.12 hours). |
| Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Up to Week 4 | The severity of clinical chemistry including liver chemistry and hematology toxicities was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for maximum clinical chemistry and hematology toxicities for oral phase (Day 1 upto Week 4) by grades have been presented. |
| Number of Participants Who Received Concurrent Medication in Overall Study Duration | Up to Week 41 | The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito-urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, anti-infectives for systemic use, sensory organs, systemic hormonal preparations excluding sex hormones, blood and blood forming organs, cardiovascular system, anti-neoplastic and immunomodulating agents, anti-parasitic products, insecticides and repellents . The participants who took medication from any of the above class of during the during the overall study duration injection phase (Day 1 until Week 41) have been presented. |
| Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Up to Week 41 | Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for Ctau defined as the concentration at the end of the dosing interval and Cmax defined as the maximum observed plasma concentration. |
| Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase | Up to Week 41 | Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for tmax defined as the time to the maximum observed plasma concentration and t½ defined as the time taken for the concentration of drug in the blood to decrease by half of the original amount. |
| Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | Up to Week 41 | The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for AUC (0-tau) by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for AUC (0-tau) by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square. |
| Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | Up to Week 41 | The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for Ctau and Cmax by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI. ). Assessments was also performed for Ctau and Cmax by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square. |
| Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | Up to Week 41 | The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for tmax and t½ by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for tmax and t½ by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square. |
| Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | Up to Week 41 | Acceptability of cabetogravir injections was assessed number of participants who had severe ISRs and ISR symptom. ISR examination for severity included an assessment of pain, pruritis, warm to touch, bruising, discoloration, erythema, swelling, induration and bump events. Common ISR Symptoms for Injection Phase included pain, erythema, nodules and any other ISRs with greater or equal to five participants. Data has been presented for the injection phase (W5-W41) by grades and needle length. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 10 centers in United states. Participants who received study medication are being followed for 52 Weeks following their last injection while those in placebo group were followed until all participants completed Week 41. The first subject's first visit was 27-Mar-2014 and the last subject's last visit was 15-May-2015.
Pre-assignment details
A total of 205 participants were screened of which 78 participants were not randomized. The remaining 127 participants were randomized to the study treatment who entered the oral and injection phase. Out of this, one participant randomized but withdrawn consent prior to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Eligible participants received matching placebo tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving matching placebo injections \[0.9 percent saline\]. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injection of placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injection consisted of 800 mg of placebo. | 21 |
| Cabotegravir Eligible participants received daily oral cabotegravir 30 mg tablets for 4 Week during the Oral Phase of the study, followed by a 1 Week washout period, to assess for safety and tolerability prior to receiving cabotegravir injections. Following safety laboratory assessments from the Oral Phase, participants entered the Injection Phase and received IM injections of cabotegravir or placebo at 3 time points at 12 Week intervals (Week 5, Week 17, and Week 29). The IM injections consisted of 800 mg of cabotegravir. | 106 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Injection Phase | Lost to Follow-up | 0 | 1 |
| Injection Phase | Physician Decision | 0 | 3 |
| Injection Phase | Protocol defined stopping criteria | 1 | 0 |
| Injection Phase | Withdrawal by Subject | 0 | 3 |
| Oral Phase | Adverse Event | 0 | 7 |
| Oral Phase | Physician Decision | 0 | 1 |
| Oral Phase | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Cabotegravir | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 35.1 Years STANDARD_DEVIATION 11.75 | 34.9 Years STANDARD_DEVIATION 11.68 | 33.7 Years STANDARD_DEVIATION 11.56 |
| Race/Ethnicity, Customized African American/African Heritage | 33 Participants | 40 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 59 Participants | 71 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 106 Participants | 127 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 105 |
| other Total, other adverse events | 18 / 21 | 100 / 105 |
| serious Total, serious adverse events | 1 / 21 | 1 / 105 |
Outcome results
Primary
Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase
Vital signs measurements were performed for HR following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.
Time frame: Baseline (Week 5) to Week 41
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 17, HR | 1.19 beats per minute | Standard Deviation 11.021 |
| Placebo | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 29, HR | 1.55 beats per minute | Standard Deviation 10.149 |
| Placebo | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 41, HR | 1.43 beats per minute | Standard Deviation 10.181 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 29, HR | 4.06 beats per minute | Standard Deviation 10.74 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 17, HR | 3.26 beats per minute | Standard Deviation 11.684 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Heart Rate (HR) in the Injection Phase | Week 41, HR | 2.73 beats per minute | Standard Deviation 11.752 |
Primary
Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase
Vital signs measurements were performed for SBP and DBP following 5 minutes of rest. Baseline was defined as the first injection at Week 5 for the injection phase. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value at Week 17, Week 29 and Week 41.
Time frame: Baseline (Week 5) to Week 41
Population: Safety population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 17, SBP | -1.52 millimeters of mercury | Standard Deviation 14.041 |
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 17, DBP | -3.10 millimeters of mercury | Standard Deviation 11.541 |
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 29, SBP | 2.80 millimeters of mercury | Standard Deviation 10.904 |
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 41, DBP | -1.19 millimeters of mercury | Standard Deviation 13.692 |
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 41, SBP, | -1.38 millimeters of mercury | Standard Deviation 14.044 |
| Placebo | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 29, DBP | -3.75 millimeters of mercury | Standard Deviation 12.781 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 41, SBP, | 1.64 millimeters of mercury | Standard Deviation 12.012 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 41, DBP | 0.01 millimeters of mercury | Standard Deviation 9.286 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 17, DBP | -0.74 millimeters of mercury | Standard Deviation 7.214 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 17, SBP | -0.66 millimeters of mercury | Standard Deviation 9.237 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 29, SBP | 2.62 millimeters of mercury | Standard Deviation 10.868 |
| Cabotegravir | Change From Baseline in Vital Sign Assessment for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in the Injection Phase | Week 29, DBP | 0.32 millimeters of mercury | Standard Deviation 8.283 |
Primary
Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase
The severity of laboratory results was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for Number of participants who experienced grade 2 or higher laboratory results in the injection phase (Week 5-Week 14) have been presented.
Time frame: Up to Week 41
Population: Safety Injection population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Creatine kinase | 3 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Aspartate aminotransferase | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Glucose | 2 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Bilirubin | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Leukocytes | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Activated prothrombin time/standard | 1 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Lipase | 1 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Carbon dioxide | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Neutrophils | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Alanine aminotransferase | 0 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Prothrombin time | 1 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Cholesterol | 1 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Urate | 1 Participants |
| Placebo | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Activated partial thromboplastin time | 1 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Urate | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Activated prothrombin time/standard | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Activated partial thromboplastin time | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Alanine aminotransferase | 2 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Bilirubin | 4 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Carbon dioxide | 1 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Cholesterol | 4 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Creatine kinase | 6 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Glucose | 7 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Leukocytes | 2 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Lipase | 10 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Neutrophils | 3 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Prothrombin time | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Grade 2 or Higher Laboratory Results in the Injection Phase | Aspartate aminotransferase | 2 Participants |
Primary
Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase
Full 12-lead ECGs included heart rate, PR, QRS, QT and QTc intervals. Measurements were taken from the participant following 5 minutes of rest in a semi-supine position. ECGs were performed at Week 5, Week 17, Week 29 and Week 41 in the injection phase (Week 5-Week 41). ECG abnormalities characterized as abnormal-not clinically significant (A-NCS) and abnormal-clinically significant (A-CS) upto Week 41 have been presented. There were no A-CS findings for ECG in the injection phase.
Time frame: Up to Week 41
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 17, A-NCS | 9 Participants |
| Placebo | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 41, A-NCS | 5 Participants |
| Placebo | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 29, A-NCS | 7 Participants |
| Placebo | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 5, A-NCS | 6 Participants |
| Cabotegravir | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 41, A-NCS | 23 Participants |
| Cabotegravir | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 5, A-NCS | 30 Participants |
| Cabotegravir | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 29, A-NCS | 27 Participants |
| Cabotegravir | Number of Participants Who Had Abnormal Electrocardiogram (ECG) Findings in the Injection Phase | Week 17, A-NCS | 34 Participants |
Primary
Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase
The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, sensory organs, systemic hormonal preparations, excluding sex hormones, blood and blood forming organs, cardiovascular system. The participants who took medication from any of the above class of during the injection phase (Week 5-Week 41) have been presented.
Time frame: Up to Week 41
Population: The randomized population was defined as all participants who met the study criteria and were randomly assigned to treatment in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase | 5 Participants |
| Cabotegravir | Number of Participants Who Recieved Injection Site Reaction (ISR) Related Concomitant Medication in the Injection Phase | 55 Participants |
Primary
Number of Participants With Any Grade 2 or Higher Event in the Injection Phase
Clinical adverse event (AE) were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41).
Time frame: Up to Week 41
Population: Safety Injection population was defined as all participants enrolled in the study who received at least one injection of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Any Grade 2 or Higher Event in the Injection Phase | 10 Participants |
| Cabotegravir | Number of Participants With Any Grade 2 or Higher Event in the Injection Phase | 75 Participants |
Comparison: Any Grade 2 or higher event, any Grade 2 or higher event Vs Cabotegravirp-value: <0.01Fisher Exact
Primary
Number of Participant With ISR for the Injection Phase Defined by Maximum Grades
Common ISR included pain, erythema, nodules and any other ISR with greater or equal to 5 participants. The number of participants who experienced pain events by needle length, swelling events by needle length, bump events by needle length for injection phase by maximum grades have been presented for the injection phase (Week 5-Week 41).
Time frame: Up to Week 41
Population: Safety Injection population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 4 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 2 | 1 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 2 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 3 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 1 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 1 | 11 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 3 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 4 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 1 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 4 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 2 | 0 Participants |
| Placebo | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 1 | 11 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 2 | 3 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 2 | 37 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 4 | 0 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 3 | 18 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 2 | 4 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 1 | 9 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR swelling, Grade 4 | 0 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR pain, Grade 1 | 31 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participant With ISR for the Injection Phase Defined by Maximum Grades | ISR Bump, Grade 4 | 0 Participants |
Secondary
Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades
The severity of clinical chemistry including liver chemistry and hematology toxicities was graded according to the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening. Data for maximum clinical chemistry and hematology toxicities for oral phase (Day 1 upto Week 4) by grades have been presented.
Time frame: Up to Week 4
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 3 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 4 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 4 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 1 | 2 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 1 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 1 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 3 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 2 | 3 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 2 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 2 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 4 | 0 Participants |
| Placebo | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 4 | 1 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 2 | 4 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 3 | 2 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 4 | 4 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 1 | 9 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 2 | 2 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Liver chemistry, Grade 4 | 1 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 1 | 4 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Hematology, Grade 2 | 1 Participants |
| Cabotegravir | Number of Participants Who Experienced Maximum Clinical Chemistry Including Liver Chemistry and Hematology Toxicities in the Oral Phase by Grades | Clinical chemistry, Grade 1 | 33 Participants |
Secondary
Number of Participants Who Received Concurrent Medication in Overall Study Duration
The concurrent medications that were consumed by participants during the injection phase were of the class nervous system, musculo-skeletal system, genito-urinary systems and sex hormones, various, respiratory system, dermatologicals, alimentary tract and metabolism, anti-infectives for systemic use, sensory organs, systemic hormonal preparations excluding sex hormones, blood and blood forming organs, cardiovascular system, anti-neoplastic and immunomodulating agents, anti-parasitic products, insecticides and repellents . The participants who took medication from any of the above class of during the during the overall study duration injection phase (Day 1 until Week 41) have been presented.
Time frame: Up to Week 41
Population: The Randomized Population comprised of all participants who met study criteria were randomly assigned to treatment in the study with the exception of any participants with documented evidence of not having consumed any amount of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Received Concurrent Medication in Overall Study Duration | 20 Participants |
| Cabotegravir | Number of Participants Who Received Concurrent Medication in Overall Study Duration | 97 Participants |
Secondary
Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase
Clinical AE were graded using the DAIDS table for grading the severity of adult and pediatric AE Version 1.0, December 2004; Clarification August 2009. The grades were: 1 (mild)=Symptoms causing no or minimal interference with usual social and functional activities; 2 (moderate)= Symptoms causing greater than minimal interference with usual social and functional activities; 3 (severe)= Symptoms causing inability to perform usual social and functional activities; 4 (potentially life threatening): Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data has been presented for any Grade 2 or higher event in the injection phase for injection phase (Week 5- Week 41).
Time frame: Up to Week 4
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Grade 2-4 AE | 4 Participants |
| Placebo | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Any AE | 8 Participants |
| Placebo | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Any SAE | 0 Participants |
| Cabotegravir | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Any AE | 56 Participants |
| Cabotegravir | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Any SAE | 0 Participants |
| Cabotegravir | Number of Participants With AE, Grade 2-4 AE and Serious Adverse Events (SAE) in the Oral Phase | Grade 2-4 AE | 24 Participants |
Secondary
Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length
Acceptability of cabetogravir injections was assessed number of participants who had severe ISRs and ISR symptom. ISR examination for severity included an assessment of pain, pruritis, warm to touch, bruising, discoloration, erythema, swelling, induration and bump events. Common ISR Symptoms for Injection Phase included pain, erythema, nodules and any other ISRs with greater or equal to five participants. Data has been presented for the injection phase (W5-W41) by grades and needle length.
Time frame: Up to Week 41
Population: Safety injection population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Warm to touch | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 1 | 3 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 2 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Severe or Grade 3 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Erythema | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Bruising | 1 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Haemorrhage | 1 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Induration | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 1, | 11 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Swelling | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 4 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 2 | 1 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Discolouration | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Mild or Grade 1 | 11 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 3 | 0 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms,needle any length,Moderate or Grade2 | 1 Participants |
| Placebo | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Bump | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Grade 4 | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 3 | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 4 | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Bruising | 11 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms,needle any length,Moderate or Grade2 | 8 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Severe or Grade 3 | 2 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 1, | 63 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 2 | 51 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 3 | 18 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pain, Grade 4 | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 1 | 15 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Discolouration | 4 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Erythema | 6 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Haemorrhage | 0 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Induration | 10 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Swelling | 15 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Bump | 12 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Warm to touch | 12 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR symptoms, needle any length, Mild or Grade 1 | 12 Participants |
| Cabotegravir | Number of Participants With Severity of ISRs and ISR Symptoms for Injection Phase Defined by Grades and Needle Length | ISR, needle any length, Pruritis, Grade 2 | 6 Participants |
Secondary
Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase
Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for AUC(0-tau) a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (i.e.12 hours).
Time frame: Up to Week 41
Population: The pharmacokinetic parameter population comprised of all participants who underwent plasma pharmacokinetic sampling and have evaluable cabotegravir parameters estimated. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase | Injection 2 | 3873.25 hour*microgram per milliliter | Geometric Coefficient of Variation 44.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase | Injection 3 | 4020.89 hour*microgram per milliliter | Geometric Coefficient of Variation 36.2 |
| Placebo | Plasma Pharmacokinetic Assessment for Area Under the Plasma Concentration-time Curve Over the Dosing Interval [AUC(0-tau)] in the Injection Phase | Injection 1 | 3414.71 hour*microgram per milliliter | Geometric Coefficient of Variation 42.5 |
Secondary
Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase
The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for AUC (0-tau) by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for AUC (0-tau) by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.
Time frame: Up to Week 41
Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI upper, Injection 1 | 2830.06 hour*microgram per milliter | Geometric Coefficient of Variation 45.6 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI upper, Injection 2 | 3536.52 hour*microgram per milliter | Geometric Coefficient of Variation 36.7 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI upper, Injection 3 | 3405.52 hour*microgram per milliter | Geometric Coefficient of Variation 35.2 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 1.5 inch Injection 1 | 3666.95 hour*microgram per milliter | Geometric Coefficient of Variation 40 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 1.5 inch Injection 2 | 4177.42 hour*microgram per milliter | Geometric Coefficient of Variation 44 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 1.5 inch Injection 3 | 4263.31 hour*microgram per milliter | Geometric Coefficient of Variation 38.9 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 2 inch Injection 1 | 2782.06 hour*microgram per milliter | Geometric Coefficient of Variation 42.6 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 2 inch Injection 2 | 3191.72 hour*microgram per milliter | Geometric Coefficient of Variation 38.5 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 2 inch Injection 3 | 3493.85 hour*microgram per milliter | Geometric Coefficient of Variation 24.1 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI lower, Injection 1 | 4103.71 hour*microgram per milliter | Geometric Coefficient of Variation 28.4 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI lower, Injection 2 | 4250.82 hour*microgram per milliter | Geometric Coefficient of Variation 49.6 |
| Placebo | Plasma Pharmacokinetic Assessment for AUC(0-tau) by Demographic Factor Body Mass Index (BMI) and Needle Length in the Injection Phase | 50 percent BMI lower, Injection 3 | 4847.07 hour*microgram per milliter | Geometric Coefficient of Variation 26.1 |
Secondary
Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase
Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for Ctau defined as the concentration at the end of the dosing interval and Cmax defined as the maximum observed plasma concentration.
Time frame: Up to Week 41
Population: Pharmacokinetic parameter population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Cmax, Injection 1 | 4.26 micrograms per milliliter | Geometric Coefficient of Variation 88.6 |
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Cmax, Injection 2 | 5.22 micrograms per milliliter | Geometric Coefficient of Variation 78 |
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Cmax, Injection 3 | 4.91 micrograms per milliliter | Geometric Coefficient of Variation 66.6 |
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Ctau, Injection 1 | 0.302 micrograms per milliliter | Geometric Coefficient of Variation 157.1 |
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Ctau, Injection 2 | 0.331 micrograms per milliliter | Geometric Coefficient of Variation 164.5 |
| Placebo | Plasma Pharmacokinetic Assessment for Concentration at the End of the Dosing Interval (Ctau) and Maximum Observed Concentration (Cmax) in the Injection Phase | Ctau, Injection 3 | 0.387 micrograms per milliliter | Geometric Coefficient of Variation 149.6 |
Secondary
Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase
The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for Ctau and Cmax by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI. ). Assessments was also performed for Ctau and Cmax by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.
Time frame: Up to Week 41
Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Cmax, Injection 1 | 6.02 micrograms per milliter | Geometric Coefficient of Variation 51.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Cmax, Injection 2 | 6.65 micrograms per milliter | Geometric Coefficient of Variation 54.8 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Cmax, Injection 3 | 6.99 micrograms per milliter | Geometric Coefficient of Variation 35.9 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Ctau, Injection 1 | 0.226 micrograms per milliter | Geometric Coefficient of Variation 159.9 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Cmax, Injection 1 | 2.99 micrograms per milliter | Geometric Coefficient of Variation 100 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Cmax, Injection 3 | 3.59 micrograms per milliter | Geometric Coefficient of Variation 68 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Cmax, Injection 2 | 6.09 micrograms per milliter | Geometric Coefficient of Variation 63.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Ctau, Injection 2 | 0.381 micrograms per milliter | Geometric Coefficient of Variation 200.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Ctau, Injection 1 | 0.394 micrograms per milliter | Geometric Coefficient of Variation 141.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Ctau, Injection 2 | 0.350 micrograms per milliter | Geometric Coefficient of Variation 193.8 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Ctau, Injection 2 | 0.312 micrograms per milliter | Geometric Coefficient of Variation 138.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for Ctau, Injection 3 | 0.334 micrograms per milliter | Geometric Coefficient of Variation 102.2 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Cmax, Injection 2 | 4.12 micrograms per milliter | Geometric Coefficient of Variation 88.4 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for Ctau, Injection 3 | 0.437 micrograms per milliter | Geometric Coefficient of Variation 193.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Cmax, Injection 1 | 4.94 micrograms per milliter | Geometric Coefficient of Variation 79.3 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Cmax, Injection 3 | 5.56 micrograms per milliter | Geometric Coefficient of Variation 65 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Ctau, Injection 1 | 0.270 micrograms per milliter | Geometric Coefficient of Variation 177.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Ctau, Injection 2 | 0.312 micrograms per milliter | Geometric Coefficient of Variation 152.4 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for Ctau, Injection 3 | 0.372 micrograms per milliter | Geometric Coefficient of Variation 150.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Cmax, Injection 1 | 2.78 micrograms per milliter | Geometric Coefficient of Variation 92.8 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Cmax, Injection 2 | 3.52 micrograms per milliter | Geometric Coefficient of Variation 92.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Cmax, Injection 3 | 3.65 micrograms per milliter | Geometric Coefficient of Variation 57.6 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Ctau, Injection 1 | 0.418 micrograms per milliter | Geometric Coefficient of Variation 93.7 |
| Placebo | Plasma Pharmacokinetic Assessment for Ctau and Cmax by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for Ctau, Injection 3 | 0.426 micrograms per milliter | Geometric Coefficient of Variation 152.1 |
Secondary
Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase
Blood samples for pharmacokinetic analysis were collected starting on the first day of the First Injection Phase prior to the injection. At each injection visit a blood sample was collected prior to the injection at Week 5, Week 17 and Week 29, 1 Week post-injection at Week 6, Week 18, and Week 30, and 12 Week post-injection at Week 17, Week 29, and Week 41. The sample collected 12 Week following each injection served as the pre-dose sample for the subsequent dosing interval. Two additional samples were collected 4 and 8 Week after the first injection (Week 9 and Week 13), and 1 additional sample was collected 6 Week following the second and third injections (Week 23 and Week 35). Assessment was carried out for tmax defined as the time to the maximum observed plasma concentration and t½ defined as the time taken for the concentration of drug in the blood to decrease by half of the original amount.
Time frame: Up to Week 41
Population: Pharmacokinetic parameter population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase | tmax, Injection 1 | 13.14 days | Standard Deviation 11.503 |
| Placebo | Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase | tmax, Injection 2 | 8.91 days | Standard Deviation 9.311 |
| Placebo | Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase | t½ , Injection 1 | 20.54 days | Standard Deviation 10.69 |
| Placebo | Plasma Pharmacokinetic Assessment for Time to Maximum Observed Concentration (Tmax), Apparent Terminal Phase Half-life for (t½) in the Injection Phase | tmax, Injection 3 | 9.25 days | Standard Deviation 7.579 |
Secondary
Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase
The median BMI was 26 kilogram per meter square. Plasma pharmacokinetic assessments were performed for tmax and t½ by BMI, either above or below the median BMI (50 percent upper and lower, where upper summary included all participants with BMI greater than or equal to the median BMI of the population and lower summary included all participants with BMI below the median BMI). Assessments was also performed for tmax and t½ by needle length (1.5 inch and 2 inch). Needle length and BMI were correlated in that the longer needle was recommended for participants with BMI greater than 30 kilogram per meter square.
Time frame: Up to Week 41
Population: Pharmacokinetic parameter population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for t½, Injection 1 | 21.26 Days | Standard Deviation 11.506 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for tmax, Injection 1 | 18.34 Days | Standard Deviation 14.987 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for tmax, Injection 2 | 8.42 Days | Standard Deviation 5.757 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for tmax, Injection 1 | 8.55 Days | Standard Deviation 5.402 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for tmax, Injection 2 | 8.62 Days | Standard Deviation 7.378 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for tmax, Injection 3 | 7.75 Days | Standard Deviation 1.845 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI lower for t½, Injection 1 | 19.54 Days | Standard Deviation 10.384 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for tmax, Injection 1 | 17.83 Days | Standard Deviation 14.008 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for tmax, Injection 3 | 8.57 Days | Standard Deviation 7.196 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 2 inch for t½, Injection 1 | 17.27 Days | Standard Deviation 4.747 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for tmax, Injection 2 | 9.20 Days | Standard Deviation 10.955 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for tmax, Injection 3 | 10.58 Days | Standard Deviation 10.139 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 50 percent BMI upper for t½, Injection 1 | 22.32 Days | Standard Deviation 11.234 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for tmax, Injection 1 | 11.33 Days | Standard Deviation 9.497 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for tmax, Injection 2 | 9.10 Days | Standard Deviation 10.408 |
| Placebo | Plasma Pharmacokinetic Assessment for Tmax and t½ by Demographic Factor BMI and Needle Length in the Injection Phase | 1.5 inch for tmax, Injection 3 | 9.53 Days | Standard Deviation 7.774 |