Safety and Tolerability of Oral Proglumide for NASH

NCT04152473 | Completed Phase 1 FDA Drug

• 2 other identifiers: 0562GU-3160
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This study is an open labelled Phase I/II clinical trial, designed to evaluate the safety and efficacy of an oral cholecystokinin (CCK) receptor antagonist, proglumide, at escalating doses in subjects with NASH. An extended use protocol has been approved for subjects completing this study that show benefit or are at risk of Liver disease progression to continue on Proglumide at 1200 mg / day for an additional 3-9 months. Subjects in the extended protocol will have telephone visits monthly and in the research unit every 3 months for safety lab tests and research blood for fibrosis analysis.

Conditions

Nonalcoholic Steatohepatitis

Keywords

NASH

Outcome Measures

Primary Outcomes (2)

• safety and toxicity

  Number of participants with drug related Toxicity will follow standard Common Terminology Criteria for Adverse Events v.5,(CTCAE) criteria protocols. Toxicity is graded according to severity for symptoms obtained on the visit review of symptoms and according to blood tests collected at each scheduled visit

  12-weeks per dose

• Recommended Phase 2 dose

  Of the 3 doses to be tested which one has the fewest Drug related toxicity

  for each dose, the number of AEs described over the 12 week period

Secondary Outcomes (1)

• Liver transaminases

  Comparison of baseline serum ALT and AST values to week 12 week values in IU

Other Outcomes (1)

• NASH score by Fibroscan

  baseline compared to week 12

Study Arms (1)

Proglumide

EXPERIMENTAL

Open labelled proglumide treated

Drug: Proglumide

Interventions

Proglumide DRUG

oral CCK receptor antagonist

Also known as: Milid

Proglumide

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ages 18 years to 85
• with radiographic imaging (by ultrasound, MRI, or CT) of fatty liver disease
• AND elevation in serum transaminases (ALT or AST).
• AND one of the following: BMI\>30, hyperlipidemia, or evidence of poorly controlled diabetes such as HgbA1C \>7
• Subjects on statins and with diabetes are eligible. Statins will be continued at the same dose for the duration of the study.
• Evidence of mild to moderate fibrosis on Fibroscan of F1 to F3 (kPa score \< 14).

You may not qualify if:

• Evidence of active alcohol use/abuse.
• Chronic viral hepatitis B or hepatitis C, autoimmune hepatitis, drug induced liver disease.
• Those with evidence of cirrhosis on exam, histologically, or imaging, and a history of liver cancer are excluded.
• Evidence of abnormal synthetic liver function including abnormal total bilirubin, platelet count \<150,000 / mm3; and abnormal prothrombin time or increased INR (international normalized ratio) (unless on warfarin)
• History of gall bladder disease with gall bladder not surgically removed
• Estimated glomerular filtration rate (eGFR of \< 90 mL/min/1.73m2
• Type 1 diabetes mellitus
• Poorly controlled diabetes, defined by hemoglobin A1C (HbA1C) \> 8, or diabetic patients that have not been on stable doses of anti-diabetic medication for at least 90 days prior to screening
• Pregnant or breast feeding
• A known preexisting medical or psychiatric condition that could interfere with the patient's ability to provide informed consent or participate in study conduct, or that may confound the study findings.
• Those found to have fibrosis score on Fibroscan of F0 or F4.

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (2)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Washington DC Veterans Affairs Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

Related Publications (2)

• Tucker RD, Ciofoaia V, Nadella S, Gay MD, Cao H, Huber M, Safronenka A, Shivapurkar N, Kallakury B, Kruger AJ, Kroemer AHK, Smith JP. A Cholecystokinin Receptor Antagonist Halts Nonalcoholic Steatohepatitis and Prevents Hepatocellular Carcinoma. Dig Dis Sci. 2020 Jan;65(1):189-203. doi: 10.1007/s10620-019-05722-3. Epub 2019 Jul 11.

  PMID: 31297627 BACKGROUND

• Rabiee A, Gay MD, Shivapurkar N, Cao H, Nadella S, Smith CI, Lewis JH, Bansal S, Cheema A, Kwagyan J, Smith JP. Safety and Dosing Study of a Cholecystokinin Receptor Antagonist in Non-alcoholic Steatohepatitis. Clin Pharmacol Ther. 2022 Dec;112(6):1271-1279. doi: 10.1002/cpt.2745. Epub 2022 Sep 27.

  PMID: 36087237 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Proglumide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Glutamine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Study Officials

• Jill P Smith, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open labelled sequential Phase I ascending dose study

Study Record Dates

• First Submitted: October 20, 2019
• First Posted: November 5, 2019
• Study Start: December 13, 2019
• Primary Completion: August 31, 2022
• Study Completion: September 9, 2022
• Last Updated: October 13, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: After the publication at the completion of the study
• Access Criteria: Available on clinicaltrials.gov website for 1 year after publication

Locations

US (2)