NCT02673619已完成2 期
A Phase 2a Study to Evaluate the Clinical Effect, Pharmacokinetics, Safety and Tolerability of Topically Applied Umeclidinium in Subjects With Primary Palmar Hyperhidrosis
Stiefel, a GSK Company1 个研究点 分布在 1 个国家目标入组 58 人开始时间: 2016年3月7日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Posterior Probability That the Response Rate is Greater Than 50%
研究概览
简要总结
Umeclidinium (UMEC) is a potent pan-active long-acting muscarinic antagonist (LAMA). It is anticipated that topical administration of UMEC will block stimulation of muscarinic receptors, thereby reducing the overproduction of sweat in subjects who suffer from hyperhidrosis. This study will assess the clinical effect, pharmacokinetics, safety and tolerability of topically applied UMEC following once daily topical administration, for 28 days, to the palms, in subjects with primary palmar hyperhidrosis. The study will also investigate if topically applied UMEC, at the highest possible concentration, will decrease palmar hyperhidrosis with a systemic anticholinergic adverse event profile similar to or below that observed with inhaled administration. This is a double blind (Sponsor unblind), repeat dose, randomized, parallel group, placebo controlled study. Study will enrol up to 55 subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent may be considered for enrolment. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
- •Non-reproductive potential defined as, Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy OR Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
- •Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and for 30 days after the last dose of study medication and completion of the follow-up visit.
- •The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
- •The subject has a HDSS score of 3 or
- •The subject has a diagnosis of primary, palmar hyperhidrosis, defined as excessive, palmar sweating of at least 6 months duration without apparent cause and with at least one of the following characteristics: Positive family history of hyperhidrosis or Hyperhidrosis is bilateral and relatively symmetrical or First episode of hyperhidrosis before 25 years of age or Cessation of focal sweating during sleep.
- •The subject has a Baseline/Day 1 gravimetric assessment of at least 150 mg sweat produced at rest, during a period of 5 minutes separately for each palm. (Measurements can be repeated up to two times on two different days, screening and/or Baseline/Day 1 visits, but subjects need to qualify on at least one occasion for each palm.)
- •The subject agrees to avoid to use nicotine-containing products (including nicotine patches) during the treatment period
- •The subject is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in protocol
排除标准
- •The subject has an unstable or life threatening cardiac disease such as: Myocardial infarction or unstable angina in the last 6 months or Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months or New York Heart Association (NYHA) Class IV heart failure
- •The subject has a diagnosis of Type 1 or Type 2 diabetes, or is receiving treatment for control of blood glucose levels.
- •The subject has a diagnosis of hyperthyroidism, as confirmed by thyroid stimulating hormone (TSH), or is receiving treatment for hyperthyroidism.
- •The subject has a diagnosis of narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study Investigator or Medical Monitor would prevent use of an anticholinergic.
- •The subject has irritation or active infection of palm area, including sweat glands.
- •The subject has a current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones that the Investigator deems clinically insignificant)
- •The subject has an ALT>2xUpper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
- •The subject has QT interval corrected for heart rate (QTc) > 450 milli second (msec) or QTc > 480 msec in subjects with Bundle Branch Block.
- •The QTc according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
- •For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Reporting and Analysis Plan (RAP).
- •The subject has a history of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist or any ingredient of the preparation.
- •The subject has had a prior surgical procedure for palmar hyperhidrosis.
- •The subject has had treatment with radiofrequency and/or microwave devices for palmar hyperhidrosis
- •The subject has had botulinum toxin injections for palmar hyperhidrosis in the last year prior to Baseline/Day 1
- •The subject has had treatment with iontophoresis for palmar hyperhidrosis within 4 weeks prior to Baseline/Day 1
- •The subject used antiperspirant on the palms within 2 weeks of the Baseline/Day 1
- •The subject is a menopausal female who has had symptoms of menopause such as sweating or flushing within 3 years of Baseline/Day 1
- •The subject has used any prohibited medication within the indicated washout period
- •The subject tested positive for any of the following at screening or within 3 months of the first scheduled dose of study medication: Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody.
- •The subject has a positive pre-study drug and/or alcohol test at screening
- •The subject has a positive test for Human immunodeficiency virus (HIV) antibody at screening.
- •The subject has participated in a clinical trial and has received an investigational product within the following time periods prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). This does not apply to UMEC when a subject who participated in the 1.85% cohort participates in the 1.15% cohort
- •The subject has had exposure to more than four investigational medicinal products within 12 months prior to the first dosing day.
- •The subject has any other condition which, in the judgment of the Investigator, would put the subject at unacceptable risk from participation in the study (e.g., subjects with renal failure).
- •The subject has clinically significant abnormalities in laboratory values which, according to the Investigator, would put the subject at undue risk due to study participation.
- •The subject has abnormal findings on screening ECG deemed clinically significant by the Investigator.
- •The subject is pregnant or lactating or is planning on becoming pregnant during the study.
研究组 & 干预措施
Umeclidinium once daily (QD) 1.85%
Experimental
Subjects will apply UMEC topically once daily (2microliter [µL]/centimeter [cm]^2) to both the hands (palm and fingers) using graduated syringe at night before bedtime for 28 days. Randomization will be 4:1 (UMEC 1.85%: vehicle)
干预措施: Umeclidinium (Drug)
Vehicle QD
Placebo Comparator
subjects will apply vehicle topical once daily (2µL/cm^2) to both the hands (palm and fingers) using graduated syringe at night before bedtime for 28 days.
干预措施: Vehicle (Drug)
结局指标
主要结局
Posterior Probability That the Response Rate is Greater Than 50%
时间窗: Baseline and Day 29
A response rate is defined as percentage of participants who achieved at least 30 percent decrease from Baseline in gravimetric sweat production at Day 29. Baseline was latest assessment prior to first dosing. A response rate of greater than 50 percent was considered to be clinically meaningful (greater than 50 percent of participants achieving at least 30 percent decrease from Baseline in gravimetric sweat production at Day 29). The posterior probability that response rate in sweat production is greater than 50 percent was analyzed. The evaluation was performed using Bayesian analysis, in which latest pre-dose value was used as Baseline.
Percentage of Participants With at Least 30 Percent Reduction From Baseline in Sweat Production at Day 29
时间窗: Baseline and Day 29
Percentage of participants at Day 29 post-treatment with at least a 30 percent reduction from Baseline in sweat production measured by gravimetry. Participants remained at rest for at least 20-30 min before the measurements in order to reduce external interference. The latest pre-dose value was considered as Baseline value. The summary of percentage of participants from both the cohorts with at least 30 percent reduction from Baseline in sweat production was presented for the average of both palms.
次要结局
- Percentage of Participants With at Least 50% Reduction From Baseline in Sweat Production at Day 29(Baseline and Day 29)
- Change From Baseline in Amount of Sweat Produced at Day 29(Baseline and Day 29)
- Percentage Change From Baseline/Day1 in Amount of Sweat Produced at Day 29(Baseline and Day 29)
- Plasma Concentration After Repeat Dosing of UMEC(Pre dose on Day 27 and 28; 3, 6, 9, 10, 12, 16, 24 hours post dose on Day 29; 36 and 48 hours post dose on Day 30)
- Maximum Plasma Concentration (Cmax)(Day 28)
- Time of the Maximum Measured Plasma Concentration (Tmax) After Repeat Dosing of UMEC(Pre dose on Day 28; 3, 6, 9, 10, 12, 16, 24 hours post dose on Day 29; 36 and 48 hours post dose on Day 30)
- Plasma Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau)(Pre dose on Day 27 and 28; 3, 6, 9, 10, 12, 16, 24 hours post dose on Day 29; 36 and 48 hours post dose on Day 30)
- Population Pharmacokinetic Profile After Repeat Dosing of UMEC(Pre dose on Day 27 and 28; 3, 6, 9, 10, 12, 16, 24 hours post dose on Day 29; 36 and 48 hours post dose on Day 30)
- Number of Participants With Abnormal Urine Analysis(Day 1, 15 and 29)
- Number of Participants With Shift of Response in HDSS Score at Day 29(Baseline and Day 29)
- Percentage of Participants With at Least 2-point Decrease From Baseline to Day 29 in HDSS Score(Baseline and Day 29)
- The Terminal Plasma Elimination Rate Constant (Lambda z)(Day 28)
- The Apparent Terminal Phase Half-life (t1/2) After Repeat Dosing of UMEC(Day 28)
- The Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration [AUC(0-t)] and AUC Over the Dosing Interval Tau, [AUC(0-tau)] After Repeat Dosing of UMEC(Pre dose on Day 28; 3, 6, 9, 10, 12, 16, 24 hours post dose on Day 29; 36 and 48 hours post dose on Day 30)
- Number of Participants With Adverse Event (AE) and Serious Adverse Events (SAE's)(Up to Day 43)
- Change From Baseline in Heart Rate(Baseline, Day 15, 27, 28 and 29)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Day 1, 15 and 29)
- Number of Participants With Abnormal Values of Chemistry Parameters Assessment as a Safety Measure(Day 1, 15 and 29)
- Change From Baseline in Body Temperature Assessment as a Safety Measure(Baseline, Day 15, 27, 28 and 29)
- Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline, Day 15, 27, 28 and 29)
- Change From Baseline in Weight(Baseline and Up to Day 29)
- Number of Participants With Local Tolerability Assessments(Day 1, 8, 15, 22, 27, 28, 29, 30, 36 and 43)
- Number of Participants With Abnormal Values of Hematological Parameters(Day 29)
研究者
研究点 (1)
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