A Phase 1, Two-part, Double-blind, Active-control, Randomized Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Repeat-Dose Cabotegravir (CAB 400 mg/mL Formulation) Long-Acting Injection Following Subcutaneous or Intramuscular Administration in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 5
- 主要终点
- Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h
研究概览
简要总结
This is an active control, randomized study to investigate the safety, tolerability and PK of repeat dose administration of long-acting CAB 400 mg/mL formulation intramuscular (IM) (gluteus medius and vastus lateralis) and subcutaneous (SC) (abdominal) injections in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This will be a double-blind (sponsor-unblind) study.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- •Participants who are overtly healthy as determined by medical evaluation.
- •A participant with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or
排除标准
- •, outside the reference range for the population being studied may be included if the investigator determines and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Participants who are negative on two consecutive tests for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), performed at Screening and within 5 days of admission to the Phase I unit, using an approved molecular test (Polymerase chain reaction [PCR]).
- •Body weight more than or equal to (>=)40 kilogram (kg) and body mass index (BMI) within the range 18 to 32 kilogram per square meter (kg/m^2).
- •Male participants are eligible to participate if they agree to use contraceptive methods and refrain from donating sperm.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (<)1 percent(%).
- •Capable of giving signed informed consent.
- •Exclusion Criteria:
- •Signs and symptoms which in the opinion of the investigator are suggestive of Coronavirus disease 2019 (COVID-19) (that is [i.e.] fever, cough etc) within 14 days of inpatient admission.
- •Contact with known COVID-19 positive person/s in the 14 days prior to inpatient admission.
- •History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- •Abnormal blood pressure as determined by the investigator.
- •Alanine transaminase (ALT) more than (>)1.5 times upper limit of normal (ULN).
- •Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Corrected QT interval (QTc) >450 milliseconds (msec).
- •A known hypersensitivity to hyaluronidases (Cohort 4h only).
- •The participant has an underlying skin disease or disorder (infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that would interfere with assessment of injection sites.
- •Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (less than or equal to [<=]325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
- •Participants considered to have insufficient musculature to allow safe administration of CAB 400 mg/mL (gluteus medius or vastus lateralis).
- •History of ongoing or clinically relevant seizure disorder within the previous 2 years, including participants who have required treatment for seizures within this time period.
- •History of or on-going high-risk behaviors that may put the participant at increased risk for Human Immunodeficiency Virus (HIV) acquisition in the opinion of the investigator. This includes participants in HIV discordant relationships, or men who report current or prior unprotected anal sex with other men and those reporting prior or current injecting drug use.
- •Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- •Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
- •The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
- •A positive pre-study drug/alcohol screen.
- •Exclusion criteria for screening electrocardiogram (ECG):
- •Heart rate: For Males <45 or >100 beats per minute (bpm), for females <50 or >100 bpm.
- •PR Interval: For males and females <120 or >220 msec.
- •QRS duration: For males and females <70 or >120 msec.
- •QT duration corrected for heart rate by Fridericia's formula (QTcF) interval: For males and females >450 msec.
- •Evidence of previous myocardial infarction.
- •Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular [AV] block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
- •Sinus Pauses >3 seconds.
- •Any significant arrhythmia which, in the opinion of the Investigator or GlaxoSmithKline (GSK)/ViiV Medical monitor, will interfere with the safety for the individual participant.
- •Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).
- •Positive HIV antibody/antigen test. Participants will be advised regarding safer sex. In the event a participant acquires HIV during the course of the study they will be required to withdraw from the study and will be referred urgently to an HIV treatment center for further management.
- •Regular use of known drugs of abuse.
- •Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.
- •Participants with a history of intolerance to or with contraindications to the use of topical non-steroidal anti-inflammatory drugs (NSAIDs) or topical steroids will be excluded from participation in Cohort 4b.
- •Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units for males or >7 units for females.
- •Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
- •The participant has a tattoo or other dermatological condition overlying the location of injection or a prior history of silicone implants (gluteal) which may interfere with interpretation of injection site reactions or administration of CAB LA.
研究组 & 干预措施
Oral Cabotegravir (CAB) 30
Participants received oral dose of CAB 30 milligram (mg) tablet once daily for Days 1 to 28 in the oral lead in phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 1 (C1) CAB 400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 1 (C1) CAB 400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Topical Non-steroidal anti-inflammatory drug (NSAID) (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Topical steroid (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Topical NSAID placebo (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Topical steroid placebo (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Topical Non-steroidal anti-inflammatory drug (NSAID) (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Topical steroid (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Topical NSAID placebo (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Topical steroid placebo (Drug)
Part 1: Cohort 4h (C4h) CAB200 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 200 mg/mL along with 5000 U of rHuPH20 sequentially.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Part 1: Cohort 4h (C4h) CAB400 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 400 mg/mL along with 5000 units (U) of recombinant human hyaluronidase PH20 (rHuPH20) sequentially.
干预措施: Recombinant human hyaluronidase PH20 (rHuPH20) (Drug)
Part 2: Cohort 5 (C5) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 400 mg of CAB 200 mg/mL approximately 12 weeks apart. The dose was matched to the volume of CAB 400 mg/mL administered earlier in the same cohort.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 2: Cohort 5 (C5) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 400 mg of CAB 200 mg/mL approximately 12 weeks apart. The dose was matched to the volume of CAB 400 mg/mL administered earlier in the same cohort.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 2: Cohort 5 (C5) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 800 mg of CAB 400 mg/mL approximately 12 weeks apart.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 2: Cohort 5 (C5) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 800 mg of CAB 400 mg/mL approximately 12 weeks apart.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4 (C4) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 400 mg and Injection 2: 100 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 1: Cohort 4 (C4) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB400 mg/mL (Injection 1: 400 mg and Injection 2: 200 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4h (C4h) CAB200 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 200 mg/mL along with 5000 U of rHuPH20 sequentially.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 1: Cohort 2 (C2) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 300 mg and Injection 2: 200 mg respectively) subcutaneously in the abdomen, 4 weeks apart, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 1: Cohort 4 (C4) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB400 mg/mL (Injection 1: 400 mg and Injection 2: 200 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4h (C4h) CAB400 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 400 mg/mL along with 5000 units (U) of recombinant human hyaluronidase PH20 (rHuPH20) sequentially.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 2 (C2) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) subcutaneously in the abdomen, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 1 (C1) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 1: Cohort 3 (C3) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 3 (C3) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 200 mg/mL (Drug)
Part 1: Cohort 4h (C4h) CAB200 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 200 mg/mL along with 5000 U of rHuPH20 sequentially.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 3 (C3) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 3 (C3) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4 (C4) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 400 mg and Injection 2: 100 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4h (C4h) CAB400 + rHuPH20
Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 400 mg/mL along with 5000 units (U) of recombinant human hyaluronidase PH20 (rHuPH20) sequentially.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 1 (C1) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4b Group 1 (C4b G1)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 2 (C2) CAB400
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) subcutaneously in the abdomen, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
Part 1: Cohort 4b Group 2 (C4b G2)
Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2.
干预措施: Cabotegravir 400 mg/mL (Drug)
Part 1: Cohort 2 (C2) CAB200
Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 300 mg and Injection 2: 200 mg respectively) subcutaneously in the abdomen, 4 weeks apart, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase.
干预措施: Cabotegravir sodium (Oral Lead In) (Drug)
结局指标
主要结局
Part 1 Injection 1: Time of Maximum Observed Plasma Concentration (Tmax) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h
时间窗: Injection 1 - Day 1 to Week 4
Blood samples were collected for Pharmacokinetic (PK) analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 1: Maximum Observed Plasma Concentration (Cmax) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h
时间窗: Injection 1 - Day 1 to Week 4
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
时间窗: Injection 2 - Day 1 to Week 52 follow-up
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 2 Injection 1: Tmax for CAB 400 mg/ml Formulation for Cohort 5
时间窗: Injection 1 - Day 1 to Week 12
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 2 Injection 2: Tmax for CAB 400 mg/ml Formulation for Cohort 5
时间窗: Injection 2 - Day 1 to Week 52 follow-up
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 2: Apparent Terminal Phase Half-life (T1/2) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
时间窗: Injection 2 - Week 4 to Week 52 follow-up
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 2: Cmax of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b
时间窗: Injection 2 - Day 1 to Week 4
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 2 Injection 2: T1/2 for CAB 400 mg/ml Formulation for Cohort 5
时间窗: Injection 2 - Week 12 to Week 52 follow-up
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 2: Terminal Absorption Elimination Rate Constant (KALA) for CAB 400 mg/ml Formulation for Cohorts 1,2,3,4 & 4b
时间窗: Injection 2 - Week 4 to Week 52 follow-up
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 2 Injection 2: KALA for CAB 400 mg/ml Formulation for Cohort 5
时间窗: Injection 2 - Week 12 to Week 52 follow-up
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 1: Plasma Trough Concentrations (Ctau) of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b & 4h
时间窗: Injection 1 - Day 1 to Week 4
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Part 1 Injection 2: Ctau of CAB 400 mg/ml Formulation for Cohorts 1,2,3,4, 4b
时间窗: Injection 2 - Day 1 to Week 4
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Part 2 Injection 1: Ctau of CAB 400 mg/ml Formulation for Cohort 5
时间窗: Injection 1 - Day 1 to Week 12
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. Ctau is the trough concentration at the end of the dosing interval. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 800mg was presented. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR and ECLAIRE studies.
Part 1 Injection 1: Area Under the Concentration Time Curve From Time Zero to Last Quantifiable Time Point (AUC(0-t)) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4, 4b and 4h
时间窗: Injection 1 - Day 1 to Week 4
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Part 1 Injection 2: AUC(0-t) of CAB 400 mg/ml Formulation for Cohorts 1, 2, 3, 4 and 4b
时间窗: Injection 2 - Day 1 to Week 4
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
次要结局
- Concentration at 24 Hours (C24) for CAB Following Oral 30 mg Administration(At 24 hours)
- Ctau for CAB Following Oral 30 mg Administration(Up to 24 hours on day 29 (Oral lead in phase))
- Cmax of CAB 200 for Cohort 4h(Injection 1 - Day 1 to Week 52 follow-up)
- Part 1 and Part 2: Number of Participants With Adverse Events (AEs) in Injection Phase and Follow up Phase(From Injection 1 day 1 up to 52 weeks follow-up)
- Part 1 and Part 2: Number of Participants With Liver Biochemistry Abnormalities in Injection Phase and Follow up Phase(From Injection 1 day 1 up to 52 weeks follow-up)
- Cmax for CAB Following Oral 30 mg Administration(Up to Day 29)
- Tmax for CAB Following Oral 30 mg Administration(Up to Day 29)
- AUC(0-t) for CAB Following Oral 30 mg Administration(Up to Day 29)
- Tmax of CAB 200 for Cohort 4h(Injection 1 - Day 1 to Week 52 follow-up)
- AUC(0-t) of CAB 200 for Cohort 4h(Injection 1 - Day 1 to Week 52 follow-up)
- Ctau of CAB 200 for Cohort 4h and in ATLAS/FLAIR Study(Injection 1 - Day 1 to Week 52 follow-up)
- T1/2 of CAB 200 & CAB 400 for Cohort 4h(Injection 1 - Day 1 to Week 52 follow-up)
- KALA of CAB 200 & CAB 400 for Cohort 4h(Injection 1 - Day 1 to Week 52 follow-up)