A Double-blind, Randomised, Placebo-controlled Phase I Trial to Investigate Safety, Tolerability and Pharmacokinetics of Single Ascending Topical Doses of GZ21T in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- AE
研究概览
简要总结
This is a double-blind, randomised, placebo-controlled trial designed to evaluate safety, tolerability, and pharmacokinetics (PK) after topical administration of single ascending doses of GZ21T in healthy volunteers.
详细描述
Participants will receive a single topical application of GZ21T or placebo:
Part A:
- Cohort 1: 25.5 mg/cm2 GZ21T or placebo will be applied to 900 cm2 of the skin, corresponding to approximately 5% body surface area (BSA) and 23 g cream.
- Cohort 2: 25.5 mg/cm2 GZ21T or placebo will be applied to 1350 cm2 of the skin, corresponding to approximately 7.5% BSA and 35 g cream.
- Cohort 3: 25.5 mg/cm2 GZ21T or placebo will be applied to 1800 cm2 of the skin, corresponding to approximately 10% BSA and 46 g cream.
- Cohort 4: 25.5 mg/cm2 GZ21T or placebo will be applied to the face, corresponding to approximately 3-3.5% BSA (540 - 630% cm2) and 16 g cream.
Participants will come for 3 visits to the research clinic for screening, treatment, and follow-up.
Sentinel dosing will be applied. All participants will be carefully monitored by clinical staff during and after IMP application and will remain at the research clinic for at least 24 hours after treatment (Day 2) for safety assessments, including safety laboratory testing, 12-lead ECG, vital signs, local tolerability, physical examination and AEs, and PK assessments.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Part A: Double-blind Part B: Open-label
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to give written informed consent for participation in the trial.
- •Healthy male or female participant aged 18 to 70 years, inclusive.
- •Body Mass Index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 at the time of the screening visit.
- •WOCBP must practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) or must agree to use a highly effective method of contraception with a failure rate of <1 % to prevent pregnancy from at least 2 weeks prior to the administration of IMP to 4 weeks after the last administration of IMP. In addition, any male partner of a female participant must, unless he is sterile (e.g., has undergone vasectomy), agree to use a condom from the first administration of IMP until 4 weeks after the last administration of IMP.
- •WOCBP must refrain from donating eggs from the first IMP administration until 3 months after the last IMP administration.
排除标准
- •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of IMP.
- •Any clinically significant abnormalities regarding physical examination, vital signs, 12- lead ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.
- •Malignancy within the past 5 years, including removal of basal cell carcinoma.
- •Any planned major surgery within the duration of the trial.
- •Any skin condition including tattoos that may limit the evaluation of e.g., local tolerability as judged by the Investigator.
- •History of chronic urticaria, known history of urticaria triggered by specific factors or currently experiencing an episode of urticaria within the past 3 months.
- •History of psoriasis, atopic eczema and similar conditions, as judged by the Investigator.
- •Prescence of body hair or tattoos on the intended application areas, which in the opinion of the Investigator could interfere with local tolerability assessments.
- •Females who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
- •Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis B and C antibodies and/or human immunodeficiency virus (HIV).
- •After 10 minutes of supine rest at the screening visit, any vital signs values outside the following ranges: - Systolic blood pressure: <90 or ≥140 mmHg, or - Diastolic blood pressure <50 or ≥90 mmHg, or - Pulse <40 or >90 bpm
- •Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the screening visit, as judged by the Investigator.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs or food with a similar chemical structure or class to GZ21T.
- •Regular use of any prescribed or non-prescribed medications, including antacids, analgesics, herbal remedies, within 2 weeks prior to the (first) administration of IMP, except occasional intake of paracetamol (maximum 2000 mg/day and not exceeding 3000 mg/week), as well as nasal decongestants without cortisone, antihistamine, or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
- •Unwillingness to abstain from the use of topical treatment (including but not limited to corticosteroids, calcineurin inhibitors, vitamin D analogues, and retinoids) at the application site within 1 week prior to Day 1 and from the use of moisturising ointment cream, emollients, oils (including shower oil) or sunscreen within 24 hours prior to Day 1 until 1 week after IMP administration.
- •Planned treatment or treatment with another investigational drug within 3 months prior to Day
- •Participants who consented and screened but were not dosed in previous clinical trials are not to be excluded.
- •Current smokers or users of nicotine products. Irregular use of nicotine (e.g., smoking, snuffing, chewing tobacco) less than 3 times per week is allowed before screening visit.
- •Positive screening result for drugs of abuse or alcohol at the screening visit or on admission to the trial site prior to the administration of the IMP. (Positive results that are expected given the participant's medical history and prescribed medications can be disregarded as judged by the Investigator.)
- •History of alcohol abuse or excessive intake of alcohol, history or presence of drug abuse including anabolic steroids, as judged by the Investigator.
- •Plasma donation within approximately 1 month of screening or blood donation (or corresponding blood loss) during the last 3 months prior to screening, at the discretion of the Investigator.
- •The Investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
研究组 & 干预措施
Part A, Cohort 1
25.5 mg/cm2 GZ21T or placebo will be applied to 900 cm2 of the skin, corresponding to approximately 5% body surface area (BSA) and 23 g cream.
干预措施: GZ21T (Drug)
Part A, Cohort 2
25.5 mg/cm2 GZ21T or placebo will be applied to 1350 cm2 of the skin, corresponding to approximately 7.5% BSA and 35 g cream.
干预措施: GZ21T (Drug)
Part A, Cohort 3
25.5 mg/cm2 GZ21T or placebo will be applied to 1800 cm2 of the skin, corresponding to approximately 10% BSA and 46 g cream.
干预措施: GZ21T (Drug)
Part A, Cohort 4:
25.5 mg/cm2 GZ21T or placebo will be applied to the face, corresponding to approximately 3-3.5% BSA (540 - 630% cm2) and 16 g cream.
干预措施: GZ21T (Drug)
Part B, Cohort 1
13 mg/cm2 GZ21T will be applied to 900 cm2 of the skin, corresponding to approximately 5% BSA and 11.7 g cream
干预措施: GZ21T (Drug)
Part B, Cohort 2
A single dose of GZ21T decided based on the results from preceding cohorts will be applied to 900 cm2 of the skin, corresponding to approximately 5% BSA
干预措施: GZ21T (Drug)
Part B, Cohort 3
A single dose of GZ21T decided based on the results from preceding cohorts will be applied to 900 cm2 of the skin, corresponding to approximately 5% BSA
干预措施: GZ21T (Drug)
结局指标
主要结局
AE
时间窗: Day 1 to Day 7
Number of reported adverse events (AEs).
Number of Reported Skin Reactions
时间窗: Day 1 to Day 7.
Local tolerability reactions, such as Erythema, swelling, pruritus, burning, blistering and urticaria, discolouration and dryness (Investigator's assessment 0-3 none/mild/moderate/severe).
Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: Day 1 to Day 7.
Number of participants in Part A with clinically significant changes from baseline in vital signs (systolic, diastolic blood pressure and pulse)
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
时间窗: Day 1 to Day 7.
Number of participants in Part A with clinically significant changes from baseline in ECG results (resting heart rate, PQ/PR, QRS, QT and QTcF).
Number of Participants With Clinically Significant Abnormal Laboratory Test Results (Haematology, Clinical Chemistry, Coagulation)
时间窗: Day 1 to Day 7.
Number of participants in Part A with clinically significant abnormal laboratory tests results (clinical chemistry, hematology and coagulation parameters).
Number of Participants With Clinically Significant Changes in Physical Examination Findings.
时间窗: Day 1 to Day 7.
Number of participants in Part A with clinically significant changes from baseline in physical examination findings.
Amount of Cream Absorbed After Single Dose Applications.
时间窗: 0-2 hours after IMP administration
Cream absorption measured on a 4-point scale: "1= not absorbed"; "2= somewhat absorbed"; "3= mostly absorbed"; "4= completely absorbed". This outcome was prespecified to be assessed only for Part B.
次要结局
- Plasma Concentrations(Day 1 to Day 7.)
- PK Parameters- AUCinf(Day 1 to Day 7.)
- PK Parameters - AUClast(Day 1 to Day 7.)
- PK Parameters - Cmax(Day 1 to Day 7.)
- PK Parameters - Tmax(Day 1 to Day 7.)
- PK Parameters - T½(Day 1 to Day 7.)