Human Immunodeficiency Virus (HIV) Infection
Conditions
Brief summary
This clinical trial aims to evaluate the bioequivalence of a single oral dose of the test drug ADC118 tablets compared with the reference drugs (ACC017 tablets and emtricitabine/tenofovir alafenamide fumarate tablets \[II\]) under fasting conditions in healthy adult Chinese participants. It will also assess the safety of the test drug. The main questions it aims to answer include: Is the rate and extent of absorption of the test drug ADC118 tablets equivalent to that of the reference drugs? What adverse events will participants experience while taking the study drugs? Researchers will compare the pharmacokinetic profiles of ADC118 tablets with those of the two reference drugs after a single dose. Participants will: Be randomly assigned to one of three treatment sequences (TRR, RTR, or RRT) In each of the three periods, after an overnight fast of at least 10 hours, take a single dose of the test drug (T) or the reference drug (R) with 240 mL of warm water Refrain from drinking water (except for the 240 mL taken with the drug) for 1 hour before and after dosing, and not eat any food for 4 hours after dosing Complete blood sample collection and safety assessments according to the protocol This study plans to enroll 48 healthy participants. It is a single-center, randomized, open-label, three-period crossover trial.
Interventions
DRUGACC118-Test
Single oral dose of ADC118 tablet, strength: 35 mg ACC017 / 200 mg emtricitabine / 25 mg tenofovir alafenamide fumarate per tablet.
DRUGReference
Single oral dose of the following tablets taken together: Two tablets of ACC017, strength: 20 mg/tablet. One tablet of Emtricitabine/Tenofovir Alafenamide Fumarate Tablets (II), strength: 200 mg emtricitabine / 25 mg tenofovir alafenamide fumarate per tablet.
Sponsors
Jiangsu Aidea Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a single-center, randomized, open-label, three-sequence, three-period, partially-replicated crossover study. Eligible participants will be randomly assigned to one of three treatment sequences: TRR, RTR, or RRT. In each period, participants will receive a single oral dose of either the test product (T: ADC118 tablets) or the reference products (R: ACC017 tablets and emtricitabine/tenofovir alafenamide fumarate tablets \[II\]) under fasting conditions, with a washout interval separating each period. All participants will receive both the test and reference interventions in a crossover manner across the three periods, with each participant receiving the test product once and the reference products twice, depending on the assigned sequence.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult males and non-pregnant, non-lactating healthy adult females, aged 18 to 55 years (inclusive) at the time of signing the informed consent form. Subjects who exceed 55 years of age during the trial will not be excluded. * Weight: males ≥ 50.0 kg, females ≥ 45.0 kg; body mass index (BMI) \[BMI = weight (kg)/height² (m²)\] between 19.0 and 26.0 kg/m² (inclusive). * Participants (including their partners) are willing to have no pregnancy plan from the screening period until 6 months after the end of the trial, voluntarily use effective contraceptive measures, and have no plans for childbearing or sperm/egg donation. * Fully understand the content of the informed consent form, voluntarily sign it, and voluntarily participate in the trial. * Able to complete the study according to the requirements of the trial protocol.
Exclusion criteria
* Subjects with a history of allergy (allergic to two or more drugs or foods), or known allergy to the investigational product or its excipients. * Subjects with any history of clinically significant disease, or history of cardiovascular, endocrine, neurological, digestive system diseases, or pulmonary, hematological, immunological, psychiatric diseases, and metabolic abnormalities. * Subjects who have undergone surgery within 3 months prior to screening, or plan to undergo surgery during the trial, and those who have undergone any surgery that could affect the absorption, distribution, metabolism, or excretion of the drug. * Subjects with abnormalities in physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory tests that are deemed clinically significant by the investigator. * Female participants who are lactating or have a positive pregnancy test during the screening period or during the trial. * Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), human immunodeficiency virus (HIV) antibody, or syphilis screening. * Subjects who have taken any other investigational drug or participated in any other medical or drug clinical trial within 3 months prior to screening. * Subjects who have received any vaccination within 1 month prior to screening. * Subjects who have donated more than 400 mL of blood or experienced significant blood loss (\>400 mL) within 3 months prior to screening, or who plan to donate blood during the trial or within one month after the end of the trial. * Subjects who have a smoking habit (average of ≥5 cigarettes per day) within 3 months prior to screening, or who are unable to abstain from using any tobacco products during the trial. * Subjects who have consumed more than 14 units of alcohol per week within 6 months prior to screening (1 unit of alcohol = 360 mL of beer, or 45 mL of spirits with 40% alcohol, or 150 mL of wine), or who are unable to abstain from alcohol during the trial, or who have a positive alcohol screening test. * Subjects with a positive drug abuse screening test, or a history of drug abuse, or who have used illicit drugs within 3 months prior to screening. * Subjects who have taken any prescription drugs, over-the-counter medications, health supplements, or herbal medicines within 14 days prior to screening. * Subjects who develop any new illness or use any new medication (including prescription drugs, over-the-counter medications, health supplements, or herbal medicines) during the period from screening to admission on Day -1. * Subjects with special dietary requirements who are unable to comply with the standardized diet. * Subjects with difficulty in blood collection or a history of needle phobia or vasovagal syncope associated with blood draws. * Subjects who are unable to complete the trial due to other reasons, or who are deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Cmax | Day 1 (pre-dose) through Day 6 (120 hours post-dose) of each treatment period | Cmax is defined as the maximum observed plasma concentration of the drug, obtained directly from the concentration-time data, following a single oral dose of the test or reference product under fasting conditions. |
| PK Parameter: AUC0-t | Day 1 (pre-dose) through Day 6 (120 hours post-dose) of each treatment period | AUC0-t is defined as the area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration, calculated using the linear trapezoidal rule. |
| PK Parameter: AUC0-∞ | Day 1 (pre-dose) through Day 6 (120 hours post-dose) of each treatment period | AUC0-∞ is defined as the area under the plasma concentration-time curve from time zero extrapolated to infinity, calculated as AUC0-t + Clast/λz, where Clast is the last measurable plasma concentration and λz is the terminal elimination rate constant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter: Tmax | Day 1 (pre-dose) through Day 6 (120 hours post-dose) of each treatment period | Tmax is defined as the time to reach the maximum observed plasma concentration (Cmax) |
| PK Parameter: AUC0-24h | Day 1 (pre-dose) through Day 2 (24 hours post-dose) of each treatment period | AUC0-24h is defined as the area under the plasma concentration-time curve from time zero to 24 hours post-dose. |
| PK Parameter: C24h | 24 hours post-dose on Day 2 of each treatment period | C24h is defined as the plasma drug concentration sampled at 24 hours post-dose. |
| PK Parameter: AUC_%Extrap | Day 1 through Day 6 of each treatment period | AUC\_%Extrap is defined as the percentage of AUC0-∞ that is due to extrapolation from the time of the last measurable concentration (Tlast) to infinity, calculated as \[(AUC0-∞ - AUC0-t) / AUC0-∞\] × 100%. |
| PK Parameter: t1/2 | Day 1 through Day 6 of each treatment period | t1/2 is defined as the plasma elimination half-life, calculated as ln(2)/λz. λz is the terminal elimination rate constant, determined by linear regression of the log-transformed plasma concentration versus time curve; the negative value of the slope represents λz. |
| Safety: Adverse Events | From signing of informed consent through study completion, up to approximately 10 weeks | Frequency, causality, severity, and expectedness of treatment-emergent adverse events (TEAEs), including Adverse Drug Reactions (ADRs), Grade ≥3 AEs, Serious Adverse Events (SAEs), Serious Adverse Drug Reactions (SADRs), and AEs leading to treatment discontinuation or early withdrawal from the trial. |
| Vital sign: Systolic blood pressure and diastolic blood pressure | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Changes from baseline in systolic blood pressure and diastolic blood pressure. |
| Vital sign: Heart rate | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Changes from baseline in heart rate. |
| Vital sign: Respiratory rate | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Changes from baseline in respiratory rate. |
| Vital sign: Oral body temperature | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Changes from baseline in oral body temperature. |
| Physical examination:skin | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in skin examination, categorized as medical history, AE, or other. |
| Physical examination: general appearance | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in general appearance examination, categorized as medical history, AE, or other. |
| Physical examination:head | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in head examination, categorized as medical history, AE, or other. |
| Physical examination:eyes | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in eyes examination, categorized as medical history, AE, or other |
| Physical examination: ears | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in ears examination, categorized as medical history, AE, or other. |
| Physical examination:oral | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline oral appearance examination, categorized as medical history, AE, or other. |
| Physical examination:throat | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in throat examination, categorized as medical history, AE, or other. |
| Physical examination:neck | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in neck examination, categorized as medical history, AE, or other. |
| Physical examination:heart | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in heart examination, categorized as medical history, AE, or other. |
| Physical examination:lungs | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in lungs examination, categorized as medical history, AE, or other. |
| Physical examination: extremities | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in extremities examination, categorized as medical history, AE, or other. |
| Physical examination: neuromuscular | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in neuromuscular examination, categorized as medical history, AE, or other. |
| Physical examination: abdomen | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Clinically significant changes from baseline in abdomen examination, categorized as medical history, AE, or other. |
| Clinical laboratory tests: Hematology | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Number of participants with clinically significant changes from baseline in hematology parameters. Parameters assessed include white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, and differential counts (e.g., neutrophils, lymphocytes, monocytes, eosinophils, basophils). |
| Clinical laboratory tests: Blood biochemistry | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Number of participants with clinically significant changes from baseline in blood biochemistry parameters. Parameters assessed include ALT, AST, alkaline phosphatase, total bilirubin, direct bilirubin, GGT, LDH, glucose, total protein, albumin, urea, creatinine, potassium, sodium, amylase, and lipase. |
| Clinical laboratory tests: Urinalysis | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Number of participants with clinically significant changes from baseline in urinalysis parameters. Parameters assessed include white blood cells, red blood cells, pH, protein, glucose, and ketones. |
| Clinical laboratory tests: Coagulation function tests | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Number of participants with clinically significant changes from baseline in coagulation function tests. Parameters assessed include prothrombin time, activated partial thromboplastin time, and international normalized ratio (INR). |
| 12-Lead Electrocardiogram (ECG) | From the date of first study drug administration to the End of Study visit (defined as 6 days after last dose) | Changes from baseline in 12-lead ECG parameters, including heart rate, PR interval, QRS duration, QT interval, and QTcF interval. |
Countries
China
Outcome results
None listed