A Phase I, Randomized, Double-Blind, Placebo Controlled MAD Study to Assess the Safety, Tolerability, PKs and Efficacy of Topical Application of YJ001 for Spray Use in Patients With DPNP
Overview
- Phase
- Phase 1
- Intervention
- YJ001 for Spray Use
- Conditions
- Diabetic Peripheral Neuropathic Pain
- Sponsor
- Zhejiang Hanmai Pharmaceutical Technology Co., Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Safety Assessments -Number of Participants With Abnormal Laboratory Values
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This Phase I, randomized, double-blind and placebo controlled study is to evaluate the safety, tolerability, and PK, and to preliminarily assess the efficacy of topically administered YJ001 in a multiple-ascending dose (MAD) fashion in the patients with DPNP. The study will be conducted at a single study center.
In this study, 2 cohorts (N=24, 12 subjects for each cohort), each cohort will consist of 10 active and 2 placebo, with approximately equal numbers of male and female subjects.
Each subject will be administered a single dose of YJ001 as multiple sprays topically on both feet and below the ankle in the morning on Day 1 and Day 2, and will be administered as twice daily doses once in the morning and the other in the evening (with an interval of 11 to 13 h) from Day 3 through Day 11.
Detailed Description
This Phase I, randomized, double-blind and placebo controlled study is to evaluate the safety, tolerability, and PK, and to preliminarily assess the efficacy of topically administered YJ001 in a multiple-ascending dose (MAD) fashion in the patients with DPNP between ages of 18 to 80 years. The study will be conducted at a single study center. In this study, 2 cohorts (N=24, 12 subjects for each cohort), the doses of which are 296 mg/administration (Cohort M1) and 414 mg/administration (Cohort M2), are planned. Each cohort will enroll approximately equal numbers of male and female subjects. The administration area is set as 450 cm2 (both feet). Each subject will be administered a single dose of YJ001 as multiple sprays (16 sprays/foot for Cohort M1, and 12 sprays/foot for Cohort M2) topically on both feet and below the ankle in the morning on Day 1 and Day 2, and will be administered as twice daily doses once in the morning and the other in the evening (with an interval of 11 to 13 h) from Day 3 through Day 11. Each cohort will consist of 12 subjects (10 active; 2 placebo), with approximately equal numbers of male and female subjects. Each cohort will be evaluated separately for safety and PK to allow for dose escalation based on stopping criteria per protocol. The Safety Review Committee (SRC), comprised of the Principal Investigator, Medical Monitor, and Sponsor's qualified designee, will convene after completion of each cohort to evaluate available safety, PK, and other relevant data. The decision whether to escalate the dose will be made for a completed cohort based on available safety data through Day 17 (5 days post the last dose), and blinded PK data \[maximum observed plasma concentration (Cmax,ss) and area under the concentration-time curve through the first 48 hours post the last dose (AUC0-48h,ss)\]. The SRC will determine whether to proceed to the next planned dose level, continue with the study and add additional safety evaluations, expand the number of subjects at the current level, reduce the dose, or stop the study. Subjects will be screened between Day -28 through Day -7, rate the scores on Numeric Rating Scale (NRS) twice daily (once in the morning and the other in the evening) from Day -7 to Day -1, and will be admitted to the clinic on Day-1. Subjects will be housed within the clinic from Day -1 through Day 17 and will be discharged on Day 17 after all scheduled study procedures have been completed. If necessary, subjects will receive a telephone follow-up 2 days post discharge for documentation of any adverse event or concomitant medication. Safety,Pharmacokinetics and Efficacy will be evaluated.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, between the ages of 18 to 80 years at screening, both inclusive.
- •Subjects voluntarily consenting for participation in the study and having signed informed consent document. Subjects are required to understand verbal and/or written English or any other language in which a certified translation of the informed consent is available.
- •Body mass index (BMI) between 19 to 42 kg/m2 (both inclusive) at screening, calculated as weight (kg)/height2 (m2). Subjects must have two feet. Each foot must have five digits. Each foot must have at least total surface area of 450 cm2 measured from below the ankle to the toes including both dorsum and plantar areas.
- •The subject is diagnosed with Type 1 or Type 2 diabetes, and has a history of DPNP for at least 3 months based on participant report or medical history.
- •The subject should have a glycemic control that has been optimized and has been stable for at least 3 months prior to randomization. The subject has used a stable regimen of antidiabetic agents (oral) and/or insulin for at least 3 months before screening.
- •Glycated hemoglobin (HbA1c) ≤ 10% at screening.
- •Participants who have a weekly mean score of at least 4 based upon the daily mean scores using 11-point Numeric Rating Scale (NRS) in the daily diary (rated twice daily, once in the morning and the other in the evening) from Day -7 through Day 1 (should be calculated from records 7 days immediately prior to study drug administration).
- •Males must not donate sperm until 90 days after last dose of study drug and must be willing to use a condom during heterosexual activity for up to 90 days after the application of the study drug.
- •Females must be either postmenopausal for at least 1 year, surgically sterile (bilateral tubal ligation \[including clip, cauterization methods and coil\], bilateral oophorectomy or hysterectomy, and needs to be confirmed follicle-stimulating hormone \[FSH\] level \>40 IU/L), or of childbearing potential either practicing true abstinence or practicing 2 effective means of contraception for at least 4 weeks prior to randomization, and until 28 days after study drug administration:
- •Intrauterine device (IUD) or IUD hormone-releasing system.
Exclusion Criteria
- •Current participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
- •History of clinically significant drug, food allergy, skin allergy, or sensitivity to drugs of the same class (e.g., 5-aminosalicylic acid, sulfasalazine, and salicylates) or known hypersensitivity to YJ001 or any of its components.
- •History of asthma. Adults with history of benign (resolved) childhood asthma may be included.
- •Any subject who suffers severe peripheral vascular disease (e.g., intermittent claudication) at screening, and is not suitable to be involved in the study as per investigator evaluation.
- •Any subject who suffers severe cardiovascular and cerebrovascular disease (e.g., severe arrhythmia, heart failure, myocardial infarction, unstable angina pectoris, atherosclerosis, stroke, sequela of stroke, etc.), severe gastrointestinal tract disease or other serious disease (e.g., cancer) which, in the opinion of the Investigator, would prevent the subject from fully participating in the study.
- •Any subject who suffers chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or multifocal motor neuropathy (MMN).
- •Any subject who has a history of moderate to severe depression, obvious neurological or mental disorder not related to neuropathic pain but may interfere with rating of pain, as well as poly neuropathy, numbness, feeling of pins and needles and weakness in extremities, other serious pain cannot be clearly differentiated from or conditions that may interfere with rating of neuropathic pain. Subjects with weakness but w/o sensory complaints may be included.
- •Any other medical, psychological, or social condition which, in the opinion of the Investigator, would prevent the subject from fully participating in the study, would represent a concern for study compliance, or would constitute a safety concern to the subject.
- •Any subject who has suffered one or more severe hypoglycemia event (defined as neurofunctional hypoglycemia that needs third-party assistance) within 6 months prior to screening.
- •Pain scores \< 3 on the NRS over twice during the one-week run-in period.
Arms & Interventions
Cohort M1 (10active, 2 placebo)
296 mg/administration
Intervention: YJ001 for Spray Use
Cohort M1 (10active, 2 placebo)
296 mg/administration
Intervention: Placebo of YJ001 for Spray Use
Cohort M2 (10 active, 2 placebo)
414 mg/administration
Intervention: YJ001 for Spray Use
Cohort M2 (10 active, 2 placebo)
414 mg/administration
Intervention: Placebo of YJ001 for Spray Use
Outcomes
Primary Outcomes
Safety Assessments -Number of Participants With Abnormal Laboratory Values
Time Frame: through study completion, an average of 1year
Observed values and changes in baseline of clinical safety laboratory parameters
Safety Assessments - Skin Reaction
Time Frame: through study completion, an average of 1year
Administration site assessment
Safety Assessments - AEs
Time Frame: through study completion, an average of 1year
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Secondary Outcomes
- Pharmacokinetics - CLr/f,ss(Day 1 - Day 28)
- Pharmacokinetics-AUC(Day 1-Day 28)
- Pharmacokinetics - tmax(Day 1-Day 28)
- Pharmacokinetics- Cmax(Day 1-Day 28)
- Pharmacokinetics - tlag(Day 1)
- Pharmacokinetics - t1/2(Day 1-Day 28)
- Efficacy evaluation indicator(Day -7 - Day 12)
- Efficacy evaluation indicators(Day -1, Day 7, Day 11)