2024-511993-55-00招募中2 期
A randomised, double-blind, multicentre, international placebo-controlled phase II study aimed at investigating the efficacy and safety of a novel modified-release tablet formulation of colesevelam hydrochloride in patients with idiopathic bile acid diarrhoea (BAD)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 21
- 主要终点
- Proportion of study participants, who are stool consistency responders at Week 8 after T1 or T2 as compared to P. A stool consistency responder is defined as a participant who experiences a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 in the 7-point Bristol Stool Form Scale (BSFS) compared with baseline.
研究概览
简要总结
The primary objective of the study is to investigate the efficacy of 2 dose regimens of the test investigational medicinal product (T) as compared to the matching placebo (P), in terms of proportion of study participants with a diagnosis of idiopathic bile acid diarrhoea (BAD) who are stool consistency responders.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Informed consent: signed written informed consent before inclusion in the study;
- •Sex and age: men/women, ≥18 years old inclusive;
- •Diagnosis or symptoms of bile acid diarrhoea: suspected or diagnosed type II (idiopathic) bile acid diarrhoea or subjects presenting with symptoms compatible with bile acid diarrhoea, including subjects with suspected functional diarrhoea or IBS-D as per Rome IV criteria, who fulfil the following criteria: a. have a fasting serum 7αC4 >46.0 ng/mL; b. have at least 4 days per week during the screening period with ≥1 bowel movement with a stool consistency of Type 6 or 7 in the 7-point BSFS;
- •Contraception (women only): women of childbearing potential must use at least one of the following highly effective methods of contraception: a. Hormonal combined oral, intravaginal, or transdermal, contraceptives for at least 2 months before the screening visit b. Progestogen-only hormonal oral, implantable, or injectable contraceptives for at least 2 months before the screening visit c. A non-hormonal intrauterine device [IUD] or an intrauterine hormone-releasing system (IUS) for at least 2 months before the screening visit d. Bilateral tubal occlusion e. A sterile sexual partner f. True abstinence, i.e., refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject. Women of non-childbearing potential or in postmenopausal status must have been in that status for at least one year. For all women of childbearing potential, serum pregnancy test result must be negative at screening;
- •Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the study;
- •Compliance with baseline diary entry: a minimum of 3 consecutive days of completed diary entries or 4 nonconsecutive days within a 7-day period are necessary;
排除标准
- •Prior and concomitant gastrointestinal diseases: a. Current or recurrent disease that could affect the ileum and the enterohepatic circulation of bile acids, including ileal resection or bypass, short bowel syndrome, previous cholecystectomy, radiation enteritis, chronic pancreatitis, known small intestine bacterial overgrowth; b. Inflammatory bowel disease, including known microscopic colitis; c. Bowel obstruction; d. Biliary obstruction; e. Acute suspected or proven infectious (viral or bacterial) gastroenteritis within the 8 weeks prior to screening; f. Acute suspected or proven gastroenteritis within the 8 weeks prior to screening; g. Positive for Clostridium difficile as detected by appropriate specific test; h. Positive for coeliac disease blood test; i. Current or recurrent diseases that could affect the colon including diverticulitis, collagenous colitis, colonic resection, toxic megacolon, fistula, perforation or abscess;
- •Physical findings: clinically relevant abnormal physical findings which could interfere with the objectives of the study.
- •Prior and concomitant diseases other than gastroenteric: a. Fasting triglycerides level above 3.4 mmol/L (300.9 mg/dL); b. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness; c. Any medical disorder that may require treatment or make the patient unlikely to fully complete the study or any condition that presents undue risk from the study medication or procedures; d. Malignancy in the last 5 years prior to screening; e. Hyperthyroidism;
- •Previous unsuccessful treatments: unsuccessfully treating BAD with bile acid sequestrants (cholestyramine, colestipol or colesevelam) unless the reason for treatment failure was due to non-compliance/lack of tolerability;
- •Prior and concomitant treatments: a. Treatment with other bile acid sequestrants must be stopped at least 3 days before screening; b. Treatment with glucagon like peptide1 or 2 receptor agonists (e.g., liraglutide) within 4 weeks before screening; c. Treatment with cyclosporine within 1 month before screening; d. Treatment with oral anticoagulants like warfarin and similar drugs within 1 month before screening; e. Any concomitant medication, which colesevelam may have an interaction with, whose administration cannot be suspended for the duration of the study and which cannot be administered separated from the study drug (at least 4 h prior to or after the administration of colesevelam); f. Any concomitant medication for diarrhoea-predominant irritable bowel syndrome within 4 weeks prior to screening; g. Treatment with antidiarrheal drugs (e.g. loperamide, bismuth subsalicylate) within 1 week prior to screening; h. Treatment with drugs with a known pharmacological activity on 5-HT4, 5-HT2b or 5-HT3 receptors (e.g., tegaserod, ondansetron, tropisetron, granisetron, dolasetron, mirtazapine cilansetron, alosetron) within 2 weeks before screening; i. Treatment with drugs affecting the function of the gastrointestinal tract, including opioids (e.g. morphine, oxycodone, codeine, methadone, fentanyl, tramadol), anticholinergic drugs (e.g., dicyclomine, hyoscyamine, propantheline), anti-nausea drugs (e.g. trimethobenzamide, promethazine, prochlorperazine, dimenhydrinate, hydroxyzine), laxative drugs (e.g. lactulose, sorbitol or polyethylene glycol preparations), prokinetic drugs (e.g. cisapride, metoclopramide, prucalopride, domperidone) within 4 weeks before screening; j. Rectal treatments (other than topical steroids for the treatment of haemorrhoids) within 2 weeks before screening; k. Treatment with immunosuppressant or immunomodulator agents including monoclonal antibodies (for instance, infliximab, adalimumab, azathioprine, 6-mercaptopurine, cyclosporine, vedolizumab, tofacitinib, filgotinib, ozanimod, etc.), within 6 weeks prior to screening; l. Treatment with ustekinumab within 16 weeks prior to screening; m. Treatment with antibiotics within 2 weeks before screening; n. Repeated treatment with non-steroidal anti-inflammatory drugs (e.g. aspirin or ibuprofen) within 7 days prior to screening. Prophylactic use of a stable dose of aspirin up to 100 mg/day for cardiac disease is permitted;
- •Inflammatory markers: C-reactive protein >1.0 mg/dL; abnormal faecal calprotectin >100 μg/g;
- •Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations’ ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study;
- •Pregnancy (women only): pregnant or lactating women or women wishing to become pregnant in the 3 months following the screening visit; positive or missing pregnancy test at screening;
- •Liver function: chronic liver disease or clinically significant liver enzyme abnormality as evidenced by elevated aspartate aminotransferase, alanine aminotransferase >2.5 times upper limit of normal or total bilirubin >1.5 times upper limit of normal;
- •Investigative drug trials: participation in experimental therapeutic trials in the last 3 months before screening;
结局指标
主要结局
Proportion of study participants, who are stool consistency responders at Week 8 after T1 or T2 as compared to P. A stool consistency responder is defined as a participant who experiences a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 in the 7-point Bristol Stool Form Scale (BSFS) compared with baseline.
Proportion of study participants, who are stool consistency responders at Week 8 after T1 or T2 as compared to P. A stool consistency responder is defined as a participant who experiences a ≥50% reduction in the number of days with at least one stool that has a consistency of Type 6 or 7 in the 7-point Bristol Stool Form Scale (BSFS) compared with baseline.
次要结局
- 01. Proportion of study participants, who are stool consistency responders at Week 2 and 4 after T1 or T2 as compared to P.
- 02. Proportion of study participants achieving remission of diarrhoea as per Hjortswang criteria, defined as <3 bowel movements per day and <1 stool per day with consistency of Type 6 or 7 in the 7-point BSFS calculated as the mean of the last 7 days prior to Week 8 after T1 or T2 as compared to P.
- 03. Proportion of study participants, who are stool frequency responders at Week 8 after T1 or T2 as compared to P. A stool frequency responder is defined as a participant, who experiences a ≥50% reduction in the number of days with ≥3 bowel movements compared with baseline
- 04. Proportion of study participants who achieve remission in urgency, defined as a score of <3 in the urgency numerical rating scale at Week 2, 4 and 8 after treatment with T1 or T2 as compared to P.
- 05. To compare between treatments the proportion of patients with and the number of adverse drug reactions after 8 weeks of treatment.
研究者
Chief Scientific Officer (CSO)
Scientific
Cosmo Technologies Limited
研究点 (21)
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