Safety, Tolerability, Efficacy Study of PUR 0110 Rectal Enema in Mild-to-Moderate Distal Ulcerative Colitis

NCT01149707 | Completed Phase 2

• 3 other identifiers: PG09 PUR 0210 0022009 017839 1829PS1617
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

Brief Summary

PUR 0110 is a 100% natural novel investigational medicinal product that has been demonstrated in several in vitro and in vivo pharmacology studies to have potent anti-inflammatory, anti-oxidative and immunomodulatory effects. This exploratory Phase 2a study is a first-in-patient study to evaluate the safety, tolerability, biomarker effect and efficacy of PUR 0110 rectal enema in patients with active mild-to-moderate distal ulcerative colitis (UC). The study is a multicenter, randomized, double-blind, parallel-group, dose-ranging, placebo-controlled study. To be eligible for inclusion into the study, patients must either be newly diagnosed or have on-going active mild-to-moderate distal ulcerative colitis of at least 3 months duration confirmed in either case by flexible sigmoidoscopy and biopsy at the Screening Visit. In addition, patients must have a modified Mayo score of ≥5 to ≤10 including a sigmoidoscopy inflammation grade and rectal bleeding scores of ≥2 each. Eligible patients will be randomly assigned to receive either PUR 0110 250 mg, 500 mg or 1000 mg or placebo rectal enema in a 1:1:1:1 ratio. Patients will self-administer the assigned study medication intrarectally once-daily at bedtime (10:00 p.m +/- 1 hour) for 2 weeks. Patients will be evaluated for safety by adverse events, clinical laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and concomitant medications. Efficacy evaluations will include the modified Mayo score, patient-defined response and remission, Investigator Assessment of Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire (IBDQ), and biomarkers of inflammation, apoptosis and total cell death, lipid peroxidation and in vivo oxidative stress, and antioxidant defense mechanisms in plasma, serum, urine, feces and biopsy tissue. Patients will have a flexible sigmoidoscopy and biopsy 12 hours after the last dose of study medication.

Conditions

Left-Sided Ulcerative Colitis; Proctosigmoiditis

Keywords

PUR 0110; PUR 0110 Rectal Enema; Distal Ulcerative Colitis; Left-Sided Ulcerative Colitis; Mild; Moderate

Outcome Measures

Primary Outcomes (1)

• Number of patients with treatment-related adverse events

  Safety \& Tolerability of PUR0110 rectal enema compared to placebo as per Incidence, nature and severity of adverse events (AEs); and abnormal clinical laboratory test results.

  At Week 2

Secondary Outcomes (12)

• Effectiveness of PUR0110 on remission rate

  At week 2

• Effectiveness of PUR0110 on clinical response rate

  At week 2

• Effectiveness of PUR0110 on subject response and remission rate

  At week 2

• Effectiveness of PUR0110 on overall Mayo score

  At week 2

• Effectiveness of PUR0110 on in each of the 4 individual sub-scores of the modified Mayo score.

  At week 2

Study Arms (4)

PUR 0110 Rectal Enema 250 mg

EXPERIMENTAL

Active treatment

Drug: PUR 0110 Rectal Enema 250 mg

PUR 0110 Rectal Enema 500 mg

EXPERIMENTAL

Active treatment

Drug: PUR 0110 Rectal Enema 500 mg

PUR 0110 Rectal Enema 1000 mg

EXPERIMENTAL

Active treatment

Drug: PUR 0110 Rectal Enema 1000 mg

Placebo Enema

PLACEBO COMPARATOR

Placebo comparator

Drug: Placebo Enema

Interventions

PUR 0110 Rectal Enema 250 mg DRUG

PUR 0110 Rectal Enema 250 mg, once-daily, intrarectally

Also known as: Active treatment arm

PUR 0110 Rectal Enema 250 mg

PUR 0110 Rectal Enema 500 mg DRUG

PUR 0110 Rectal Enema 500 mg, once-daily, intrarectally

Also known as: Active treatment arm

PUR 0110 Rectal Enema 500 mg

PUR 0110 Rectal Enema 1000 mg DRUG

PUR 0110 Rectal Enema 1000 mg, once-daily, intrarectally

Also known as: Active treatment arm

PUR 0110 Rectal Enema 1000 mg

Placebo Enema DRUG

Placebo Enema, once-daily, intrarectally

Also known as: Placebo arm

Placebo Enema

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatient males and females between 18 and 75 years.
• Females of child bearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin) at screening and must be sexually inactive (abstinent) for 3 months prior to dosing and throughout the study or be using one of the following acceptable methods of contraception:
• barrier methods (condom, diaphragm with spermicide);
• Intrauterine device (IUD) in place for at least 3 months;
• surgical sterilization of the partner (vasectomy for at least 6 months); or
• hormonal contraceptives for at least 3 months prior to dosing. \[Female subjects of childbearing potential must be advised to remain sexually inactive or maintain the same method of contraception for ≥7 days following the end of dosing of study treatment\]
• Patients newly diagnosed or with ongoing active distal ulcerative colitis of \>3 months duration, confirmed by flexible sigmoidoscopy during screening, and extending 5 to 50 cm from the anal margin. Sigmoidoscopy must be conducted within not more than 3 +/- 1 days before the Baseline (Day 0) Visit.
• Patients with ongoing active distal ulcerative colitis of ≥3 months duration must be on a stable dose of oral mesalamine (5-ASA) for ≥2 months before the Baseline (Day 0) Visit.
• Modified Mayo Score (Disease Activity Index) of ≥5 to ≤10 at Baseline, including a sigmoidoscopic inflammation grade score of ≥2 and a rectal bleeding score ≥2.
• Negative stool test at screening to rule out parasites, bacterial pathogens and Clostridium difficile.
• Able and willing to fill in (maintain) daily diary cards from Day -7 to Day 21 of the study.
• Able to provide voluntary written informed consent prior to initiation of screening, must be capable of following the verbal and written study instructions, and be able to commit to the return visits during the entire period of the study.

You may not qualify if:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, or psychiatric disease, that could compromise patient's ability to participate in the study, and/or interfere with absorption of the study drug or the interpretation of the study data.
• Patients with a diagnosis of Crohn's disease.
• Patients with a modified Mayo score of ≥11 at the Screening (Day -7 \& Day -3) Visits.
• Patients at immediate or significant risk of toxic megacolon; those with bowel stricture, colonic dysplasia, adenoma or carcinoma.
• Use of botanical treatments and supplements for ulcerative colitis within 14 days prior to the Baseline Visit.
• Patients with any enteric pathogens, ova or parasites, or Clostridium difficile toxin in stool.
• Female patients with a positive pregnancy test or lactating at the Screening/Baseline Visits.
• History of allergic reaction or hypersensitivity to spinach, spinach tablet, spinach powder or spinach extract; and to latex, molds and mushrooms.
• History of gout, pseudogout or hyperuricemia, or kidney stones.
• History of pseudoallergic hypersensitivity to the food color additives, tartrazine (E102), sunset yellow (E110) and FD \& C Blue No.1 (Brilliant blue FCF; E133), allergic asthma, aspirin intolerance, and severe or multiple allergies.
• Past medical history of significant gastrointestinal surgery including but not limited to colostomy, ileostomy, or previous colonic surgery other than appendectomy.
• Patients with anatomical abnormalities of the colon, e.g., short bowel or other abnormalities.
• Patients with any current infectious, ischemic, or immunologic disease with gastrointestinal involvement.
• Patients with a history of failure to retain enemas.
• Use of antibiotics for reasons related to the primary diagnosis or for other gastrointestinal-related conditions within 14 days of Baseline Visit.

Sponsors & Collaborators

• PurGenesis Technologies Inc.: lead

Study Sites (6)

PurGenesis Investigational Site

Jena, 07740, Germany

Location

PurGenesis Investigational Site

Köln-Merheim, 51109, Germany

Location

PurGenesis Investigational Site

Ludwigshafen, 67067, Germany

Location

PurGenesis Investigational Site

Minden, 32423, Germany

Location

PurGenesis Investigational Site

Oelde, 59302, Germany

Location

PurGenesis Investigational Site

Werden, 45239, Germany

Location

MeSH Terms

Conditions

Proctocolitis; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Proctitis; Colonic Diseases; Intestinal Diseases; Sigmoid Diseases; Rectal Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Theophilus J Gana, MD, PhD

  Devonian Health Group Inc.

  STUDY DIRECTOR

• Michael Rünzi, Prof. Dr. med.

  Essen-Werden, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2010
• First Posted: June 23, 2010
• Study Start: June 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: June 20, 2015
• Last Updated: May 1, 2018

Record last verified: 2018-04

Locations

DE (6)