A Phase I Study of QLS12010 Capsules: Safety, Tolerability, PK, PD, and Food Effects in Healthy Adults and Moderate to Severe Atopic Dermatitis Patients

Официальное название

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effects of Single and Multiple Ascending Doses of QLS12010 Capsules in Healthy Adult Participants and Participants With Atopic Dermatitis

Обзор

The goal of this clinical trial is to evaluate the safety, tolerability, PK, and PD of single and multiple ascending doses of QLS12010 Capsules and the effect of food on their PK profiles in healthy adult participants and participants with atopic dermatitis. This study consists of four parts: Part A is a single ascending dose (SAD) study, once sufficient safety and PK data are obtained from the SAD cohorts, the SMC will determine the dosage of initial cohort in Part B, which consists of three multiple ascending doses (MAD) cohorts of QLS12010 Capsules. Part C is a randomized, open-label, two-cycle, crossover food effect study under fasting and fed (high-fat meal) conditions. Part D is to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and preliminary efficacy of QLS12010 Capsules following multiple oral administrations in adult participants with atopic dermatitis (AD).

Вмешательства

• Препарат QLS12010
  QLS12010 oral capsule(s)
• Препарат Placebo
  Matching placebo oral capsule(s)

Первичные конечные точки

• Incidence and severity of treatment emergent Adverse Events as assessed by CTCAE v5.0 [Срок оценки: up to approximately 1 month]

Вторичные конечные точки (12)

• Area under the curve plasma concentration from time zero to last measurable concentration [AUC(0-last)] [Срок оценки: up to approximately 1 month]
• Area under the curve plasma concentration from time zero to infinity [AUC(0-∞)] [Срок оценки: up to approximately 14 days]
• Maximum observed plasma concentration (Cmax) [Срок оценки: up to approximately 1 month]
• Time to maximum observed plasma concentration (Tmax) [Срок оценки: up to approximately 1 month]
• Terminal elimination half-life (t1/2) [Срок оценки: up to approximately 1 month]
• Apparent clearance (CL/F) [Срок оценки: up to approximately 1 month]
• Apparent volume of distribution (Vz/F) [Срок оценки: up to approximately 1 month]
• Mean residence time (MRT) [Срок оценки: up to approximately 1 month]
• Changes and percentage changes from baseline in Eczema Area and Severity Index (EASI) scores [Срок оценки: at Weeks 1, 2, 3, 4, 5, and 6]
• Changes and percentage changes from baseline in Investigator's Global Assessment (IGA) scale [Срок оценки: at Weeks 1, 2, 3, 4, 5, and 6]
• Changes and percentage changes from baseline in weekly mean scores of Peak Pruritus Numerical Rating Scale (PP NRS) [Срок оценки: at Weeks 1, 2, 3, 4, 5, and 6]
• Changes and percentage changes from baseline of body surface area (BSA) affected by lesions [Срок оценки: at Weeks 1, 2, 3, 4, 5, and 6]

Критерии участия

Inclusion Criteria for Parts A-C:

• Males and females aged 18-45 (inclusive),
• Weight: ≥ 50 kg for males and ≥ 45 kg for females, body mass index (BMI): 18.0-30.0 kg/m2 (inclusive),

Inclusion Criteria for Part D:

• Female or male participants between the ages of 18 to 75 years of age.
• Chronic AD diagnosed by the criteria of Hannifin and Rajka that has been present for at least 6 Months before the Screening Visit.
• At screening and baseline: EASI score ≥ 16, vIGA-AD™ score ≥ 3, and BSA affected by AD ≥ 10%;
• The weekly mean score of PP NRS ≥ 4 prior to the first administration (with assessment results for at least 4 days during the week before the first administration \[D-7 to D-1\]);
• As judged by the investigator, within 6 months prior to screening, the patient had an inadequate response to topical medication therapy.

General Exclusion Criteria:

• Participants with diseases that should be excluded as judged by the investigator at screening, including but not limited to the nervous system, psychiatric system, cardiovascular system, blood and lymphatic system, immune system, respiratory system, digestive system, urinary system, metabolic and skeletal system disorders,
• The 12-lead ECG at screening shows QTcF (QT corrected using Fridericia's formula) > 450 ms. If QTcF is > 450 ms, the 12-lead ECG should be repeated 2 more times (at least 3 min apart), and the mean of the 3 measurements will be used to determine whether the participant meets the inclusion criteria,
• Participants who smoke more than 5 cigarettes per day on average within 6 months before screening or are currently using e-cigarettes,
• Participants who consume more than 14 units of alcohol per week (1 unit = 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine) within 6 months before screening or have a positive breath alcohol test at screening,
• Participants who have donated more than 400 mL of blood within 3 months or more than 200 mL of blood within 4 weeks before screening, or plan to donate blood during the study,
• Participants who have received any strong inhibitor or inducer of CYP3A4 within 4 weeks before screening,
• Participants who have received any prescription drugs, OTC drugs, traditional medicines, and dietary supplements within 2 weeks before the first dose or 5 half-lives (whichever is longer).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University Third Hospital — Пекин

Идентификаторы

NCT: NCT06946641 · QLS12010-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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