An Open-label, Long-term Study to Assess the Immunogenicity of Linaclotide Administered Orally to Adult Patients With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 828
- 试验地点
- 74
- 主要终点
- Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum
研究概览
简要总结
The primary objective of this study is to assess the potential of LINZESS® (linaclotide) treatment to induce the development of anti-drug antibodies (ADAs). The secondary objectives are to provide additional evidence supporting the long-term safety and efficacy of linaclotide in adult irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) participants and to evaluate lower doses of linaclotide.
详细描述
This study includes up to a 3-week Screening Period, followed by a 52-week treatment period. Participants with CIC meeting the entry criteria received linaclotide 145 μg capsules, orally, once daily and participants with IBS-C meeting the entry criteria received linaclotide 290 μg capsules, orally, once daily. Participants with intolerable Adverse Events (AEs), following resolution of the AEs, could be randomized to receive 290 μg, 145 μg, or the lower dose of 72 μg linaclotide oral capsules for IBS-C; and 145 μg or 72 μg for CIC. Participants who experienced further intolerable AEs after the randomization could be transitioned to open-label 72 μg linaclotide.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants meet the Rome III criteria for IBS-C or CIC:
- •IBS-C Criteria: the participant must meet the following 2 criteria (A and B).
- •A. IBS Criteria: The participant must have abdominal pain or discomfort at least 3 days per month in the 3 months before diagnosis (with symptom onset at least 6 months before diagnosis) associated with 2 or more of the following:
- •Improvement with defecation.
- •Onset associated with a change in frequency of stool.
- •Onset associated with a change in form (appearance) of stool. B. Stool Consistency Requirement: During the 3 months before diagnosis in the absence of laxative or enema use, the patient has hard or lumpy stools (Bristol Stool Form Scale [BSFS] score 1 or 2) with at least 25% of bowel movements (BMs) and has loose or mushy stools (BSFS 5 or 6) with <25% of BMs.
- •CIC Criteria: the participant must meet the following 3 criteria (A, B, and C):
- •A. Participant meets 2 or more of the following criteria for 3 months before the diagnosis with symptom onset at least 6 months before diagnosis:
- •Straining during at least 25% of defecations.
- •Lumpy or hard stools in at least 25% of defecations.
- •Sensation of incomplete evacuation for at least 25% of defecations.
- •Sensation of anorectal obstruction/blockage for at least 25% of defecations.
- •Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor).
- •Fewer than 3 defecations per week. B. Loose stools are rarely present without the use of laxatives. C. Insufficient criteria for irritable bowel syndrome. (The criteria for IBS are provided in Point A under IBS Criteria, above).
- •Participant meets the colonoscopy requirements, which are modified from the Summary of the US-Multi-Society Task Force on Colorectal Cancer and other Colonoscopy Requirements.
- •Participant has successfully completed protocol procedures (with no clinically significant findings).
排除标准
- •At Day 1 visit, the participant reports having 6 or more spontaneous bowel movements (SBMs) in the week prior to screening.
- •At Day 1 visit, the participant reports having any SBMs that were watery (BSFS=7) or more than 1 SBM that was mushy (BSFS=6) in the week prior to screening.
- •Participant has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility.
- •Participant has any protocol excluded or clinically significant medical or surgical history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments.
- •Participant has ever received linaclotide as a treatment (including commercially-available product) or has been randomized into any clinical study in which linaclotide was a treatment. (participant who enrolled into linaclotide clinical studies conducted prior or during this study but failed to be randomized are eligible for the current study).
- •Participant has ever received plecanatide, SP-333, or has participated in a plecanatide clinical study.
研究组 & 干预措施
LINZESS® 145 μg (CIC, Open Label)
LINZESS® (linaclotide) 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period.
干预措施: Linaclotide (Drug)
LINZESS® 290 μg (IBS-C, Open Label)
LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period.
干预措施: Linaclotide (Drug)
LINZESS® 290 μg (IBS-C, Double Blind)
Following participation in the Open Label Treatment Period, LINZESS® 290 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable.
干预措施: Linaclotide (Drug)
LINZESS® 145 μg (IBS-C, Double Blind)
Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable.
干预措施: Linaclotide (Drug)
LINZESS® 72 μg (IBS-C, Double Blind)
Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable.
干预措施: Linaclotide (Drug)
LINZESS® 145 μg (CIC, Double Blind)
Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable.
干预措施: Linaclotide (Drug)
LINZESS® 72 μg (CIC, Double Blind)
Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable.
干预措施: Linaclotide (Drug)
LINZESS® 72 μg (CIC, Dose-reduced Open Label)
Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with CIC.
干预措施: Linaclotide (Drug)
LINZESS® 72 μg (IBS-C, Dose-reduced Open Label)
Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with IBS-C.
干预措施: Linaclotide (Drug)
结局指标
主要结局
Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum
时间窗: Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks)
Participants who met either of the following criteria: 1) treatment-induced ADA-positive (≥ 1 postbaseline ADA-positive sample) for baseline ADA negative or ADA-undetermined participants or 2) treatment-boosted ADA-positive (≥ 1 postbaseline ADA-positive sample with titer values ≥ 4-fold the baseline titer value) for baseline ADA-positive participants were reported as a ADA positive responder.
次要结局
- Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC)(Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period))
- IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C(Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period))
- Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C)(Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period))
- Number of Participants With Recurrence of Diarrhea(From first dose in the Double-blind Treatment Period to Week 52)
- Number of Participants With Recurrence of Intolerable Diarrhea(From first dose in the Double-blind Treatment Period to Week 52)
- Time to First Recurrence of Diarrhea(From first dose in the Double-blind Treatment Period to Week 52)
- Change From Baseline in Participant's Assessment of Constipation Severity(Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period))
- Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C(Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period))
- Percentage of Participants With Treatment Emergent Adverse Events (TEAE)(From first dose of study treatment up to Week 52)
- Time to First Recurrence of Intolerable Diarrhea(From first dose in the Double-blind Treatment Period to Week 52)