A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Proof-of-Concept Study of GIC-1001 for the Management of Visceral Pain in Subjects Undergoing Sedation-Free, Full Colonoscopy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 308
- 试验地点
- 14
- 主要终点
- Measurements of Visceral Pain, Using a 100-mm Visual Analog Scale (VAS)
研究概览
简要总结
GIC-1001 is a novel, orally-administered, colonic analgesic drug developed as an alternative to i.v. sedation during full colonoscopy. It will be evaluated for efficacy and safety in a multi-center, randomized, double-blind, placebo controlled, dose-ranging, proof of concept Phase 2a trial. Up to 240 patients will receive one of 3 doses of GIC-1001 or its matching placebo. A pharmacokinetic evaluation will be carried out on a subset of patients (N: 24).
详细描述
- Study Objectives
1.1 Primary objective: The primary objective of this Phase IIa study is to establish clinical Proof-of-Concept (POC) by providing clinically and statistically significant evidence that GIC-1001 is safe and effective in managing visceral pain in male and female patients who undergo sedation-free, full colonoscopy for preventive purposes.
1.2 Secondary objectives: Secondary objectives will include the selection of the optimal dose of GIC-1001 from a safety/efficacy ratio point of view, establish a preliminary safety profile of the drug in patients, and obtain a preliminary general efficacy profile of GIC-1001 by assessing various secondary endpoints 2. Study Endpoints
2.1 Primary endpoints:
Visceral pain will be assessed using a 100-mm VAS, measured at various times and anatomical segments (N: 8) throughout the colon, i.e.:
- Prior to intra-rectal insertion of the endoscope;
- After insertion through the anus;
- After passage through the rectosigmoid segment;
- Immediately after passage through the splenic flexure;
- Immediately after passage through the hepatic flexure;
- Once the caecum is reached;
- Immediately after passage through the splenic flexure during scope withdrawal; and
- At the end of the procedure, once the colonoscope has been completely removed. Any additional episodes of pain experienced by the patient will also be assessed using the 100-mm VAS scale.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written Informed Consent obtained.
- •Males or females.
- •Aged 40-75 years.
- •Indication for full colonoscopy for colorectal cancer screening or investigation, including subjects presenting suggestive symptoms and who need a differential diagnosis.
- •Colonoscopy naïve subjects, i.e. who never underwent colonoscopy before, will be eligible, as well as non-naïve subjects who have previously undergone unsedated colonoscopy , or who had sedated colonoscopy at least 10 years prior (i.e. ≥ 10 years) to enrolment
- •Eligible for a procedure without sedation.
- •Able to complete questionnaires and use a Visual Analog Scale (VAS), including sufficient English, French or Spanish speaking skills as well as adequate eyesight and hearing
- •BMI ≥ 19, BMI ≤ 40 kg/m2.
排除标准
- •Known allergy or intolerance to trimebutine (Modulon® or generic).
- •Known allergy or intolerance to sulfur-containing drugs (e.g. N-acetylcysteine or captopril).
- •Previous gastrointestinal or gynecologic surgery, e.g. ileostomy, pelvic surgery,; however, patients with an appendectomy are eligible.Patients who have had a tubal ligation at least 10 years prior (i.e. ≥ 10 years) to enrolment are also eligible.
- •Diagnosed Inflammatory Bowel Disease (IBD).
- •Visceral hypersensitivity conditions such as Irritable Bowel Syndrome (IBS).
- •Clinically significant renal and/or hepatic impairment.
- •History of peritonitis.
- •Known severe diverticular disease.
- •Severe diverticulosis as documented by prior imaging series
- •Known or suspected stenosis of the colon.
- •Chronic pain syndrome such as fibromyalgia and endometriosis.
- •Any clinically-relevant abnormality identified on the screening, history, physical examination, 12-lead ECG or laboratory examination, which would, in the Investigator's opinion, preclude the administration of investigational drug product, GIC1001
- •Unexpected and significant visceral pain reported by subject prior to colonoscopy.
- •Diagnosed clinically significant psychiatric illness, including severe anxiety disorders that may affect the subject's perception of visceral pain or ability to participate in the study.
- •Patient is a lactating female.
- •Female is of childbearing potential sexually active who are unwilling or unable to use an acceptable method of contraception (which includes oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, use of a condom by the sexual partner or sterile sexual partner) throughout the duration of the study and 1 month following study completion.
- •Female is of childbearing potential, sexually abstinent who does not agree to continue abstinence or to use one of the acceptable methods of birth control should sexual activity commence.
- •Any serious medical condition that could increase the risk of adverse reactions with trimebutine.
- •Participation in another experimental drug trial within 30 days of randomization.
研究组 & 干预措施
GIC-1001 low dose
GIC-1001 , 250 mg TID during 3 consecutive days + a last, 10th dose in the morning of Day 4 (colonoscopy day)
干预措施: GIC-1001 (Drug)
GIC-1001 mid-dose
GIC-1001 , 375 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
干预措施: GIC-1001 (Drug)
GIC-1001 , high dose
GIC-1001 , 500 mg TID during 3 consecutive days + a 10th dose in the morning of day 4 (colonoscopy day)
干预措施: GIC-1001 (Drug)
GIC-1001 matching placebo
Placebo, TID during 3 consecutive days, + a 10 th dose in the morning of day 4 (colonoscopy day)
干预措施: GIC-1001 (Drug)
结局指标
主要结局
Measurements of Visceral Pain, Using a 100-mm Visual Analog Scale (VAS)
时间窗: Assessed at different anatomical locations: (1) before colonoscopy, (2) insertion of scope in anus, (3) at rectosigmoid flexure, (4) at splenic flexure, (5) at hepatic flexure, (6) at caecum, (7) at splenic flexure on way back, (8) after colonoscopy.
The Primary Outcomes Measure was the pain VAS 100-mm AUC (0mm = no pain; 100mm = worst pain), constructed from serial pain VAS measurements performed during colonoscopy. At least 8 pain VAS measurements were made, and the length of the colonoscope inserted (or removed on the way out) was recorded at every measurement. The X-axis of the VAS versus anatomical locations was defined accordingly: each VAS value corresponded to a relative length of inserted colonoscope (d/2Lc) of the X axis, where d was the actual length of the inserted colonoscope and 2Lc represented twice the total length of the colon examined (Lc). Before scope insertion the X value equaled zero. Once the caecum was reached, the X value was 0.5. Upon complete removal of the endoscope, the X value was 1. This allowed standardization of colonic length between study subjects. Visceral pain AUC (mm) was calculated from all serial measurements, where the length of inserted colonoscope determined the VAS measurement's location
次要结局
- Colonoscopy Completion Rate (%)(Number of patients during trial with a complete colonoscopy, where the scope has reached the caecum during the colonoscopy. Range of duration of colonoscopy 5.00- 50.10 minutes.)
- Time to Caecum(From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.)
- Safety-Plasma Concentrations of Trimebutine and N-Desmethyl-Trimebutine(Day 4 prior to colonoscopy.)
- Total Examination Time (Colonoscopy)(From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.)
- Endoscopist's Perception of Colonoscopy- Adequacy of Analgesia, Difficulty of Insertion and Withdrawal(From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.)
- Endoscopist's Perception of Colonoscopy- Amount of Colonic Spasm on Insertion and Withdrawal(From the time of introduction of the colonoscope, to removal of colonoscope. Range of duration of colonoscopy 5.00- 50.10 minutes.)
- Patient's Willingness to Repeat Experience(Post-colonoscopy- during subject recovery)
- Subject Satisfaction and Acceptability of the Colonic Analgesia - Patient's Global Impression of Abdominal Pain(Post-colonoscopy- during subject recovery)