Double-blind, Placebo-controlled, Randomised, Parallel-group Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Twice Daily Intra-anal Application of NRL001-cream for 14 Days.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 主要终点
- Recumbent and standing blood pressure and pulse rate
研究概览
简要总结
The study is being conducted to evaluate the safety and tolerability after single and repeated twice daily intra-anal applications of 1mL NRL001 cream in stepwise increasing concentrations.
详细描述
Single-centre, randomised, placebo-controlled, double-blind, repeated dose study in healthy male and female volunteers, comprising up to six sequential dose groups receiving 1 mL doses of an investigational cream formulation containing 0.50, 0.75, 1.00, 1.50, 2.00 and 2.50% w/w NRL001. Doses were to be investigated in stepwise increasing fashion. Progression to a higher dose-step required completion of the previous dose-step without safety limiting findings. Each dose-step was to be investigated in 12 subjects; in each dose-group, subjects assigned to active treatment were to be studied in parallel with subjects assigned to placebo in double-blind fashion with random (9:3) treatment assignment. Each subject was to be studied for one study period with double-blind investigational treatment (1 mL of an investigational cream formulation containing NRL001 or matched placebo) twice daily from the morning of D01 to the afternoon of D14; this phase was to be preceded by a single-blind placebo control day (D-1) with administration of placebo in the morning and afternoon.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females (only females of non-child-bearing potential or of child-bearing potential while taking medically appropriate contraception)
- •Caucasian
- •35 to 60 years of age (included)
- •BMI: between 22 and 26 kg.m-2
- •BW: between 50 and 100 kg
- •Willing and able to provide written informed consent
排除标准
- •General - all subjects
- •Previous participation in the trial
- •Participation in any other trial during the last 90 days
- •Donation of blood or plasma within the last 90 days before recruitment
- •History of any clinically relevant allergy
- •Presence of acute or chronic infection
- •Presence or history of any relevant medical condition or disease (as evaluated on the basis of medical history, physical examination, recumbent and standing blood pressure, treadmill ergometry, clinical laboratory tests [haematology, clinical chemistry, urinalysis, serology])
- •Presence or history of migraine, frequent headaches, Raynaud phenomenon, urinary urge, signs and symptoms of prostatism
- •Presence or history of regular/habitual diarrhoea or constipation; previous anal surgery or trauma, anal fissures, rectal disorders
- •Resting systolic blood pressure > 145 or < 90 mmHg, diastolic blood pressure > 95 or < 50 mmHg
- •Positive treadmill ergometry test
- •Resting pulse (PR) or electrocardiographic heart rate (HR) < 55 bpm
- •ECG: AV-block (AV-block grade I included), QT > 480 msec, QTc > 450 msec, sick-sinus syndrome
- •Positive hepatitis (HBs-Ag or HBc-Ab, HCV-Ab) or HIV serology test
- •History of alcohol or (social) drug abuse
- •Positive alcohol or urine drug test
- •Daily consumption of > 30 g alcohol
- •Smoking more than 15 cigarettes/day or equivalent of other tobacco products
- •Use of prohibited medication
- •Suspicion or evidence that the subject is not reliable
- •Suspicion or evidence that the subject is not able to make a free consent or to understand the information detailed in the Subject Information sheet.
- •All females
- •Positive pregnancy test
- •Lactating
- •Premenopausal women : not using contraception which is judged adequate and sufficient in the opinion of the clinical investigator
研究组 & 干预措施
NRL001 cream 0.5%w/w
0.5%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 0.5%w/w (Drug)
NRL001 cream 0.75% w/w
0.75%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 0.75%w/w (Drug)
NRL001 cream 1.0% w/w
1.0%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 1.0%w/w (Drug)
NRL001 cream 1.5% w/w
1.5%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 1.5%w/w (Drug)
NRL001 cream 2.0% w/w
2.0%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 2.0%w/w (Drug)
NRL001 cream 2.5% w/w
2.5%w/w NRL001 (1R,2S-methoxamine) 1 mL, twice daily administration (morning and afternoon) for 14 days (study Days D1 to D14).
干预措施: NRL001 cream 2.5%w/w (Drug)
结局指标
主要结局
Recumbent and standing blood pressure and pulse rate
时间窗: 17 days
BP and pulse taken lying and standing at screening, on control day and profiling days
Ambulatory 24 hour BP monitoring
时间窗: 17 days
Ambulatory 24 hour BP monitoring on control day and profiling days
12-lead digital resting ECG
时间窗: 17 days
12-lead digital resting ECG at screening, on control day and profiling days
3-lead ambulatory 24 hour ECG monitoring
时间窗: 17 days
24 hour HOLTER monitoring at screening, on control day and profiling days
次要结局
- Adverse events(17 days)
- Plasma concentrations of NRL001(17 days)
- Well being(17 days)