A Three-Arm, Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Safety and Efficacy of Once-Daily and Twice-Daily Dosing of a Novel Hydrocortisone Acetate 90 mg Suppository Formulation Administered with the Sephure® Suppository Applicator in Subjects with Ulcerative Colitis of the Rectum CHS1221
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 114
- 试验地点
- 14
- 主要终点
- To evaluate the efficacy of two dosage regimens of the study drug (90 mg hydrocortisone suppository) administered with Sephure suppository applicator compared to placebo in the treatment of UC of the rectum using the Modified Mayo Score.
研究概览
简要总结
Thisis a Three-Arm, Randomized, Placebo-Controlled, Double-Blind Phase 3 Study toEvaluate the Safety and Efficacy of Once-Daily and Twice-Daily Dosing of aNovel Hydrocortisone Acetate 90 mg Suppository Formulation Administered withthe Sephure® Suppository Applicator in Subjects with Ulcerative Colitis of theRectum.
Ulcerative colitis (UC), an inflammatory bowel disease (IBD),is a chronic disease which is characterized by diffuse mucosal inflammation. It usuallybegins in the rectum and the lower colon but may also spread continuously to involve the entire colon.Approximately 907,000 individuals in the United States (US) are affected by UC,with an incidence rate of 12.2 per 100,000 population per year.
Cristcot HCA LLC has developed a suppository formulation containing90 mg of hydrocortisone acetate (equivalent to 80 mg hydrocortisone base) persuppository. This is paired with a unique applicator (Sephure suppository applicator) to optimizedelivery of the suppository into the rectum and reduce the potential for the suppository to be expelled.This targeted therapy for UC of the rectum will reduce exposure of healthy gastrointestinaltissue to medication unnecessarily.
Additionally, the ease and hygiene associated with the use ofthe Sephure suppository applicator may promote better subject compliance to the medication.
The present study will evaluate the safety and efficacy oftwo dosage regimens of the study drug (90 mg hydrocortisone acetate suppository with Sephuresuppository applicator) compared with placebo in the treatment of UC of the rectum. UC of therectum is defined as subjects with UC extending to no more than 15 cm (5.9 inches) proximal to theanal verge. The study will only enroll subjects with a Modified Mayo Score (without physicianglobal assessment) of 3-8, and Modified Mayo sub-scores of 1-3 for stool frequency, 0-2 forrectal bleeding, and 2-3 for
colonoscopy at screening. The study will also evaluatesystemic exposure to hydrocortisone and hydrocortisone acetate following administration of the studydrug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Males or non-pregnant, non-lactating females aged 18 years and older.
- •Able to provide a signed informed consent.
- •Confirmed diagnosis of active UC of the rectum, extending no more than 15 cm (5.9 inches) proximal to the anal verge as assessed by colonoscopy performed at Visit
- •Note: Subjects may have a history of more extensive UC (e.g., pancolitis), but have active disease only in the rectum at the time of enrollment.
- •Modified Mayo sub-score for stool frequency of 1-3 at Screening Visit (Visit 1) and Baseline Visit (Visit 3).
- •Modified Mayo colonoscopy sub-score of 2-3 at Colonoscopy (Visit 2) as determined by Central Reading.
- •Modified Mayo Total Score (without physician global assessment) of 3-
- •Females of childbearing potential must be either sexually inactive (abstinent) for 21 days prior to the first dose and willing to be sexually inactive throughout the study or must be using one of the following acceptable methods of birth control: a) Surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for a minimum period of 1 month prior to screening; b) Intrauterine device in place for at least 1 month prior to screening; c) Barrier methods (condom, diaphragm) with spermicide for at least 21 days prior to screening and willing to continue throughout the study; or d) Hormonal contraceptives for at least 6 weeks prior to screening.
- •Postmenopausal females with amenorrhea for at least 12 months prior to screening.
- •Subjects willing to abstain from receiving anal sex, anal bleaching, anal waxing, etc.
- •Availability of all the screening assessment results, such as: serum pregnancy test (for females of childbearing potential), medical history, concomitant medication, AEs, vital signs, physical examination, electrocardiogram (ECG), documented colonoscopy assessment, complete blood count, clinical chemistry and serology, urinalysis and stool test results.
- •Subjects may be allowed to be re-screened for the study after consultation and approval from the medical monitor but may be enrolled (randomized) only once.
排除标准
- •1.No colonic mucosal inflammation (absence of active disease) within 15 cm (5.9 inches) proximal to the anal verge as assessed using the colonoscopy performed at Colonoscopy Visit (Visit 2).
- •2.Colonic mucosal inflammation extending beyond 15 cm (5.9 inches) proximal to the anal verge as assessed using the colonoscopy performed at Colonoscopy Visit (Visit 2).
- •3.Preliminary endoscopic sub-score of 0 or 1 as assessed by the Investigator using the colonoscopy performed at Colonoscopy Visit (Visit 2).
- •4.Endoscopic sub-score of 0 or 1 as assessed by the Central Reading using the colonoscopy performed at Colonoscopy Visit (Visit 2).
- •5.History or current diagnosis of bacterial or other infectious colitis, radiation-enteritis and radiation-proctitis, Crohn’s disease, collagenous colitis and indeterminate colitis.
- •6.Prior gastrointestinal surgery except appendectomy, cholecystectomy, and hernia.
- •7.Concomitant active gastrointestinal disease (except Irritable Bowel Syndrome) or distortion of intestinal anatomy.
- •8.Bleeding hemorrhoids at the time of enrollment.
- •9.History of recurrent diverticulitis and/or diverticulitis at the time of enrollment.
- •10.History of recurrent pancreatic disease.
- •11.Uncontrolled, previously diagnosed type 1 or 2 diabetes mellitus.
- •12.Uncontrolled abnormal thyroid function.
- •13.Mean value for triplicate sitting SBP >160 mm Hg and/or DBP >100 mm Hg after at least a 5- minute seated rest at the Screening visit.
- •The Investigator or the treating physician is allowed to adjust background blood pressure medication(s) to lower blood pressure values in order for the subject to be re-assessed for enrollment eligibility.
- •Clinically significant ECG abnormality at screening that requires further diagnostic evaluation or intervention (e.g., new, clinically significant arrhythmia or a conduction disturbance).
- •Serum hemoglobin levels <7.5 g/dL.
- •Indication of impaired liver function as shown by an abnormal liver function profile at Screening (e.g., repeated values of aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≥ 2 × the upper limit of normal).
- •Renal disease manifested by serum creatinine >2.0 mg/dL.
- •History of avascular necrosis of hip.
- •History or signs/symptoms of or positive test result at screening for cytomegalovirus, tuberculosis, human immunodeficiency virus, hepatitis B or C infection.
- •History or signs/symptoms of ocular herpes simplex or ocular varicella zoster infection.
- •History of malignant disease, with the exception of basal cell carcinoma; squamous cell carcinoma in situ of the skin; cervical carcinoma in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to screening.
- •Diagnosis of Addison’s disease, congenital adrenal hyperplasia, or other form of adrenal insufficiency.
- •Subjects with abnormal response to the ACTH stimulation test performed at the screening visit (Visit 1).
- •Active systemic infection.
- •Toxic megacolon, fistula, perforation, or abscess.
- •History of uncontrolled psychiatric disorders or seizure disorders.
- •History of non-responsive UC to steroid treatment.
- •History of drug or alcohol abuse within the last 6 months.
- •Alcohol abuse is defined as more than 14 drinks per week for men and more than 7 drinks per week for women.
- •Other current diagnosis of severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral diseases.
- •History of evidence of any medical condition that would, in the opinion of the Investigator, make the subject unsuitable for the study.
- •Positive stool test result at screening for enteric pathogens, Clostridium difficile, or presence of ova and parasites.
- •Vaccination with live vaccine within 28 days prior to randomization.
- •However, attenuated vaccine is allowed.
- •Allergies to hydrocortisone acetate or to any other ingredients of the investigational product.
- •Taking a permitted medication outside of the permitted criteria (Section 5.7.1).
- •Taking a prohibited medication (Section 5.7.2).
结局指标
主要结局
To evaluate the efficacy of two dosage regimens of the study drug (90 mg hydrocortisone suppository) administered with Sephure suppository applicator compared to placebo in the treatment of UC of the rectum using the Modified Mayo Score.
时间窗: End of treatment
次要结局
- The following secondary objectives will be evaluated hierarchically with Baseline (Day 1/Visit 3) compared to End of Treatment (Day 29/Visit 7) and then Follow Up (Day 15/Visit 5):(Reduction of stool frequency.)