A Proof of Concept Study of Pradigastat in Patients With Functional Constipation

NCT ID: NCT04620161

Last Updated: 2022-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-22
• Study Completion Date: 2022-06-03

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of pradigastat 20 and 40 mg as compared to placebo in patients with Functional Constipation.

Detailed Description

This multicenter, randomized, placebo-controlled, double-blind study is designed to demonstrate the efficacy, safety and tolerability of pradigastat relative to placebo across 2 doses (20 and 40 mg) for up to 6 weeks (4-week treatment, 2-week Follow-up) in patients with Functional Constipation.

The primary endpoint is the change from baseline in the number of weekly spontaneous bowel movement (SBM), the key secondary endpoint is the change from baseline in the number of weekly complete spontaneous bowel movement (CSBM).An SBM is defined as a stool not induced by rescue medication, whereas a CSBM is defined as an SBM associated with a sensation of complete evacuation.

Summary of Protocol Amendments:

• Original Protocol: 06 January 2020
• Amendment 1: 30 July 2020 (Reason: To respond Health Authority requests)
• Amendment 2: 05 March 2021 (Reason: Sponsor decided to amend the protocol. Key changes: inclusion/exclusion criteria, criteria for Discountinuation from study/Discontinuation from Study Medication, adding the instruction for evaluating and managing diarrhea AEs. )

Conditions

Functional Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pradigastat Tablets 20mg

The patients in this arm will receive one tablet a day of Pradigastat 20mg and one tablet a day of Pradigastat 40mg matching placebo

Group Type: EXPERIMENTAL

Pradigastat Tablets 20mg

Intervention Type: DRUG

20mg, once daily, oral administration

Pradigastat Tablets 40mg matching Placebo

Intervention Type: DRUG

once daily, oral administration

Pradigastat Tablets 40mg

The patients in this arm will receive one tablet a day of Pradigastat 40mg and one tablet a day of Pradigastat 20mg matching placebo

Group Type: EXPERIMENTAL

Pradigastat Tablets 40mg

Intervention Type: DRUG

40mg, once daily, oral administration

Pradigastat Tablets 20mg matching Placebo

Intervention Type: DRUG

once daily, oral administration

Placebo

The patients in this arm will receive one tablet a day of Pradigastat 20mg matching placebo and one tablet a day of Pradigastat 40mg matching placebo

Group Type: PLACEBO_COMPARATOR

Pradigastat Tablets 20mg matching Placebo

Intervention Type: DRUG

once daily, oral administration

Pradigastat Tablets 40mg matching Placebo

Intervention Type: DRUG

once daily, oral administration

Interventions

Pradigastat Tablets 20mg

20mg, once daily, oral administration

Intervention Type: DRUG

Pradigastat Tablets 40mg

40mg, once daily, oral administration

Intervention Type: DRUG

Pradigastat Tablets 20mg matching Placebo

once daily, oral administration

Intervention Type: DRUG

Pradigastat Tablets 40mg matching Placebo

once daily, oral administration

Intervention Type: DRUG

Other Intervention Names

ANJ908 20mg; ANJ908 40mg; ANJ908 20mg matching Placebo; ANJ908 40mg matching Placebo

Eligibility Criteria

Inclusion Criteria

1. Written informed consent must be obtained before any assessment is performed.

2. Male and female patients aged 18 to 70 years of age, inclusive.

3. Patients with FC as defined by the ROME IV diagnostic criteria for FC.

Diagnostic criteria for FC*:

• Must include 2 or more of the following:

1. Straining during more than one-fourth (25%) of defecations

2. Lumpy or hard stools (Bristol Stool Form Scale 1 or 2) more than one-fourth (25%) of defecations

3. Sensation of incomplete evacuation more than one-fourth (25%) of defecations

4. Sensation of anorectal obstruction/blockage more than one-fourth (25%) of defecations

5. Manual maneuvers to facilitate more than one-fourth (25%) of defecations (such as digital evacuation, or support of the pelvic floor)

6. Fewer than 3 SBMs per week

• Loose stools are rarely present without the use of laxatives
• Insufficient criteria for irritable bowel syndrome (IBS). *Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.

4. Patient has less than 3 SBMs/week within 2 weeks prior to the Screening Visit.

Exclusion Criteria

6. Patient must agree that after the Visit 2 (Run-in Visit) they will discontinue any prohibited medications, laxatives (prescription and over-the-counter), supplemental fibers, or traditional medicine taken for abdominal symptoms or constipation as defined per protocol except the rescue medication, provided by the study site and following the Investigator's instructions for its use. Patient should not take rescue medication (bisacodyl) on the calendar day before and the calendar day of the start of the Treatment Period (Visit 3). If the wash-out criteria are not achieved on Visit 3, the Visit could be postponed once.

7. Patient must agree to use and comply with the diet guidance provided in applicable Chronic Constipation Treatment Guideline starting after the Screening Visit and during the study until End of Study.

8. Ability of patient to swallow tablets.

9. A co-operative attitude and ability to perform all study related procedures and to correctly use the diary.

1. Patient with history of surgical resection of stomach, gallbladder, small intestine, large intestine, and bariatric surgery (excluding resection of appendicitis and benign polyp).

2. Patient with history or current affection of inflammatory bowel disease (Crohn's disease or ulcerative colitis) and celiac disease.

3. Patient with diagnosis of IBS (constipation, diarrhea, or mixed).

4. Patient with history or current ischemic colitis.

5. Patient currently with infectious enteritis or enterocolitis. Patients with asymptomatic diverticulosis, diagnosed during the colonoscopy can be enrolled, unless previous history of diverticulitis.

6. Patient currently with hyperthyroidism or hypothyroidism (unless adequately treated), or patients who have a thyroid-stimulating hormone outside of the laboratory reference range at Visit1.

7. Patient with apparent mechanical obstruction (ie, patient with ileus caused by hernia).

8. Patient has a structural abnormality of the GI tract or a disease or history of a condition that can affect GI motility.

9. Patient has ever had any of the following diseases or conditions that can be associated with constipation: pseudo-obstruction, colonic inertia, megacolon, megarectum, bowel obstruction, descending perineum syndrome, solitary rectal ulcer syndrome, and systemic sclerosis.

10. Patient currently affected by constipation due to anorectal disease, affecting the anorectal area such as anal fissure, anorectal fistulas, hemorrhoidal disease Grade III and IV, and bleeding hemorrhoids.

11. Patient currently has both unexplained and clinically significant alarm symptoms (lower GI bleeding, rectal bleeding or heme-positive stool, iron-deficiency anemia or any unexplained anemia, or weight loss) or systemic signs of infection or colitis.

12. Patient currently affected by drug-induced constipation.

13. Patient with constipation due to other organic disease.

14. Patient currently affected by active peptic ulcer (ie, disease that is not adequately treated or stable with therapy).

15. In the case of a female, the one currently affected by endometriosis or uterine adenomyosis.

16. Patient with uncontrolled severe depression, anxiety, or any eating disorder considered by the Investigator to influence drug evaluation.

17. Patient has a potential central nervous system cause of constipation (eg, Parkinson's disease, spinal cord injury, and multiple sclerosis.).

18. Patients with uncontrolled and unstable diabetes mellitus with reported episodes of hypoglycemia within 1 year prior to Screening or history of diabetic neuropathy.

19. Patient with history of abuse of drug or alcohol within 1 year before consent acquisition, or with current abuse.

20. Patient with history of or current diagnosis of any cancer (except for nonmelanoma skin cancer which has been removed) diagnosed less than 5 years prior to Screening. Patients with cancer in full remission more than 5 years after diagnosis are acceptable.

21. Patient with major surgery or any other condition that may require use of narcotic drugs or general anesthesia within 60 days of Screening and during the study.

22. Any clinically significant abnormality identified by physical examination, electrocardiogram (ECG) or laboratory tests, which in the judgment of the Investigator would compromise the patient's safety or successful participation in the clinical study, or any of the following laboratory findings:

1. Male hemoglobin < 12 g/dL (< 120 g/L) and female hemoglobin < 10 g/dL (< 100 g/L) at Screening.

2. Male serum creatinine ≥ 1.5 mg/dL and female serum creatinine ≥ 1.4 mg/dL, or creatinine clearance ≤ 60 mL/min based on calculation using the Cockcroft-Gault formula: ([140-age in years] × weight in kg)/(72 × [creatinine in mg/dL]). For women, multiply result by 0.85.

3. Active liver disease and/or significant abnormal liver function defined as aspartate aminotransferase > 2 × upper limit of the normal (ULN) and/or alanine aminotransferase > 2 × ULN and/or total bilirubin > 1.5 × ULN.

4. Patient with stool blood positive at Screening.

23. Patient currently affected by clinically significant cardiovascular disease, respiratory disease, kidney disease, hepatic disease, GI disease (excluding FC), hematology disease, endocrine disease, hemorrhagic disease, or neural/mental disease or other disease or condition that might, in the judgment of the Investigator, place the patients at undue risk or potentially compromise the results of interpretation of the study results.

24. Patient with history of drug allergy to any active or inactive ingredient of pradigastat.

25. Patients who are vegetarian or vegan.

26. Pregnant or nursing (lactating) women.

27. Women of childbearing potential, unless they are using effective methods of contraception during study.

28. Male, who are attempting to naturally father a child or donate sperm.

29. Patients who have received an investigational drug within 30 days or 5 half-lives (whichever is greater) prior to the Screening Visit.

30. Patients participating to another clinical study at any time during this study. Studies that require consent only to store data and that do not require Follow-up are not considered to be observational or interventional and are exempted from this exclusion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Covance

INDUSTRY

Sponsor Role: collaborator

Anji Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Meyers, M.D.

Role: STUDY_CHAIR

Anji Pharma

Locations

Advanced Clinical Research-Meridian

Meridian, Idaho, United States

Evanston Premier Healthcare Research

Evanston, Illinois, United States

Jubilee Clinical Research

Las Vegas, Nevada, United States

Long Island Gastrointestinal Research Group LLP

New York, New York, United States

PMG Research of Charleston

Mt. Pleasant, South Carolina, United States

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Quanzhou First Hospital

Quanzhou, Fujian, China

Southern Medical University Nanfang Hospital

Guangzhou, Guangdong, China

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

People's Hospital of Zhengzhou

Zhengzhou, Henan, China

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Huai'an First People's Hospital

Huai'an, Jiangsu, China

Nanjing First Hospital

Nanjing, Jiangsu, China

Affiliated Hospital of Jiangsu University

Suzhou, Jiangsu, China

Yangzhou First People's Hospital

Yangzhou, Jiangsu, China

Pingxiang People's Hospital

Pingxiang, Jiangxi, China

Siping Central People's Hospital

Siping, Jilin, China

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Ruijin Hopsital

Shanghai, Shanghai Municipality, China

Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University

Hangzhou, Zhejiang, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Huzhou Central Hospital

Huzhou, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Countries

United States; China

Other Identifiers

ANJ908C2101

Identifier Type: -

Identifier Source: org_study_id