Single Ascending Dose, Food Effects and Drug-Drug Interactions of ACC017 Tablets in Healthy Adult Participants

NCT06278389 | Unknown Phase 1

• 2 other identifiers: ADYY-ACC017-101CTR20240167
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this clinical trial is to investigate the safety and tolerability of single ascending dose ACC017 tablets in Chinese healthy adult participants. This study aims to address the following major questions:

• Recommended dosage for ACC017 tablets used in phase Ib/IIa trial;
• The pharmacokinetic (PK) characteristics of single dose ACC017 tablets;
• The effect of food (FE) on the PK of ACC017 tablets;
• Drug-drug interactions (DDIs) when ACC017 tablets are co-administered with emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) tablets (II).

Conditions

Healthy Adult Participants

Outcome Measures

Primary Outcomes (13)

• Frequency, causality, severity, and expectedness of adverse events (AEs)

  Includes Adverse Drug Reactions \[ADRs\], Grade 3 and above AEs, and Serious Adverse Events \[SAEs\], Serious Adverse Drug Reactions \[SADRs\], AEs resulting in treatment interruptions, AEs resulting in early withdrawal from the trial, and AEs of Special Interest \[AESI\]

  Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

• ACC017 PK parameter: Cmax (after a single mono-drug administration under the fasting condition)

  Cmax is defined as the maximum observed concentration of drug

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: C24h (after a single mono-drug administration under the fasting condition)

  C24h is defined as the plasma drug concentrations sampled 24 hours-post dose (C24h)

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: AUC0-t (after a single mono-drug administration under the fasting condition)

  AUC0-t is defined as area under the plasma concentration-time curve from time zero to the time of the last measurable plasma concentration

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: AUC0-∞ (after a single mono-drug administration under the fasting condition)

  AUC0-∞ is defined as AUC from time zero to infinity

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: Tmax (after a single mono-drug administration under the fasting condition)

  Tmax is defined as the time to reach Cmax

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: t1/2 (after a single mono-drug administration under the fasting condition)

  Half-life

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: Vz/F (after a single mono-drug administration under the fasting condition)

  Apparent volume of distribution during terminal phase after oral administration

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: CL/F (after a single mono-drug administration under the fasting condition)

  Apparent total plasma clearance of drug after oral administration

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: λz (after a single mono-drug administration under the fasting condition)

  Terminal elimination rate constant

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: AUC_%Extrap (after a single mono-drug administration under the fasting condition)

  Percentage of AUCinf due to extrapolation from Tlast to infinity

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: MRT0-t (after a single mono-drug administration under the fasting condition)

  MRT0-t is defined as the mean retention time from time zero to the time of the last measurable plasma concentration

  Day 1 through Day 8 of Stage 1

• ACC017 PK parameter: MRT0-∞ (after a single mono-drug administration under the fasting condition)

  MRT0-∞ is defined as MRT from time zero to infinity

  Day 1 through Day 8 of Stage 1

Secondary Outcomes (20)

• Vital signs: temperature

  Baseline and Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

• Vital sign: pulse

  Baseline and Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

• Vital signs: blood pressure

  Baseline and Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

• Vital signs: respiration

  Baseline and Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

• Electrocardiogram (ECG): heart rate

  Baseline and Day 1 through Day 8 of Stage 1; Day 1 through Day 8 and Day 15 through Day 22 of Stage 2

Study Arms (2)

Stage 1: ACC017 and placebo

EXPERIMENTAL

The trial is conducted sequentially from the low-dose cohorts, namely, 5 mg, 20 mg, 40 mg, 80 mg, 120 mg and 160 mg（tentative), respectively. Participants are given a single dose of ACC017 tablets or placebo under the fasting condition.

Drug: ACC017 tablets

Stage 2: ACC017 and FTC/TAF (Descovy）

EXPERIMENTAL

Stage 2 is a single center, randomized, open-label FE and DDI study with a tentative dose of 40 mg. The stage was planned to enroll 12 healthy participants (both male and female) who are randomly assigned to either the fasting-postprandial or postprandial-fasting arm at a 1:1 ratio. Eligible healthy participants are admitted on D-1 and received a single oral dose of ACC017 tablets on the day of administration of each cycle under the fasting or postprandial condition with a washout period of 7 days during the two-week period. After completing the washout of the second cycle, participants are assessed by the investigator to enter into the DDI study and receive a single oral dose of ACC017 tablets with FTC/TAF tablets under the fasting condition.

Drug: ACC017 tablets; Drug: Emtricitabine and Tenofovir Alafenamide Fumarate Tablets

Interventions

ACC017 tablets DRUG

ACC017 tablets 5 mg, 20 mg, 40 mg, 80 mg, 120 mg, and 160 mg (tentative) with matching placebo

Also known as: ACC017/Placebo

Stage 1: ACC017 and placebo; Stage 2: ACC017 and FTC/TAF (Descovy）

Emtricitabine and Tenofovir Alafenamide Fumarate Tablets DRUG

Participants received a single oral dose of ACC017 tablets with emtricitabine and tenofovir alafenamide fumarate tablets under the fasting condition.

Also known as: Descovy

Stage 2: ACC017 and FTC/TAF (Descovy）

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Volunteering to sign the informed consent and able to follow protocol-defined procedural requirements;
• Aged 18 to 55 years (inclusive);
• Male weighing ≥ 50.0 kg, female weighing ≥ 45.0 kg, and body mass index (BMI) = weight(kg)/height\^2 (m\^2) within the range of 18.5\~26 kg/m\^2 (inclusive);
• Women of child-bearing potential (WOCBP) or men without a birth plan (including sperm or egg donation) and agreeing to use effective contraception (including one or more non-pharmacological contraceptives or non-heterosexual sexual activity in daily life) from 1 month prior to informed consent up to 3 months after the last dose of the study medication;
• No history of significant medical or surgical illness, and normal results on vital signs, physical examination, 12-lead electrocardiogram (ECG), laboratory tests, chest X-ray and abdominal ultrasound examination during the screening period, or minor deviations from normal reference values that are not clinically significant in the judgment of the investigator.

You may not qualify if:

• Occurrence or persistence of clinically significant abnormal conditions, including but not limited to cardiovascular, respiratory, gastrointestinal (any history of gastrointestinal disorders affecting the absorption of medications), urinary, hematologic and lymphatic, endocrine, musculoskeletal, immune, and neuropsychiatric disorders;
• Possible or definite allergic reaction to the study drug, placebo, or any of the excipients contained, as judged by the investigator, or allergy (multiple drug and food sensitivities), or a history of allergic disease (e.g., asthma, urticaria, and eczematous dermatitis, etc.);
• Acute illness, such as respiratory tract infections requiring antibiotic treatment, occurring from screening until study drug administration;
• Inability to tolerate venipuncture, or history of needle-sickness or blood-sickness, or blood donation including component blood or significant blood loss (≥400 mL) or receipt of blood transfusion within 3 months prior to screening, or planning to donate blood during the trial period;
• Dysphagia, or surgery within 6 months prior to screening, or surgery planned during the trial, or surgery that interferes with the absorption, distribution, metabolism, or excretion of the medication;
• Smoking an average of \>5 cigarettes per day within 3 months prior to screening, or inability to stop using any tobacco-based product during the trial period;
• Average weekly alcohol consumption greater than 14 units (1 unit of alcohol ≈ 360 mL of beer, or 45 mL of 40% (alcohol by volume) spirits, or 150 mL of wine) within 3 months prior to screening or inability to discontinue use of any alcohol-containing product during the trial period, or with a positive breath test for alcohol at screening;
• Excessive consumption of tea, coffee, and/or caffeinated beverages (more than 8 cups on average per day, 1 cup ≈ 250 mL) within 3 months prior to screening, or inability to stop consuming tea, coffee, and/or caffeinated beverages during the trial period;
• Consumption or drinking of dragon fruit, mango, grapefruit, popcorn, or foods or beverages prepared from the aforementioned fruits, or foods or beverages containing xanthines, caffeine, or alcohol (including chocolate, tea, coffee, cola, and cocoa), or any other special diet that interferes with the absorption, distribution, metabolism, or excretion of the drug, within 48 hours prior to administration of the study medication;
• With special dietary requirements, or cannot accept a uniform diet；
• Use of strong or moderate CYP3A inhibitors (e.g., clarithromycin, telithromycin, ketoconazole, itraconazole and nefazodone, etc.) or strong CYP3A4 inducers (e.g., rifampicin, efavirenz, carbamazepine, phenobarbital, phenytoin, pioglitazone, St. John's wort, and glucocorticoids, etc.) within 28 days or 5 half-lives (whichever is longer) before screening；
• Use of strong or moderate UGT1A inhibitors (e.g., silybin, ritonavir, atazanavir, quinidine, diclofenac, mycophenolic acid, and osimertinib, etc.) or strong UGT1A1 inducers (e.g., rifampicin, carbamazepine, phenobarbital, and phenytoin, etc.) within 28 days or 5 drug half-lives (whichever is longer) before screening;
• Use of any prescription drugs, over-the-counter drugs or Chinese (herbal) medicines within 14 days or 5 drug half-lives (whichever is longer) prior to screening；
• Vaccination (e.g., SARS-CoV-2 virus vaccine, and hepatitis B virus vaccine, etc.) within 1 month before screening, and are not suitable for enrollment as assessed by the investigator；
• Positive for hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody, or Tponema pallidum (Tp) antibody at screening；

Sponsors & Collaborators

• Jiangsu Aidea Pharmaceutical Group Co., Ltd.: lead
• Chengdu Aidea Pharmaceutical Technology Co., Ltd: collaborator

Study Sites (1)

Beijing Ditan Hospital Capital Medical University

Beijing, 100015, China

RECRUITING

MeSH Terms

Interventions

Emtricitabine; emtricitabine tenofovir alafenamide

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Fujie Zhang, M.D., Ph.D.

  Beijing Ditan Hospital

  PRINCIPAL INVESTIGATOR

• Chaoying Hu, Ph.D.

  Beijing Ditan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Qin, M.D., Ph.D.

CONTACT

025-83193135; qinh@aidea.com.cn

Juan Yang, M.Sc.

CONTACT

025-83193135; yangjuan@aidea.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 26, 2024
• Study Start: January 24, 2024
• Primary Completion: April 23, 2024
• Study Completion: April 23, 2024
• Last Updated: March 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)