Effect of Non-Alcoholic Steatohepatitis (NASH) on the Pharmacokinetics of 99mTechnetium-Mebrofenin

NCT02235233 | Completed Phase 1

• 2 other identifiers: 13-33622R01GM041935
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to investigate the effect of NASH (non-alcoholic steatohepatitis) on the disposition of 99mTechnetium(Tc)-mebrofenin and to relate changes in 99mTc-mebrofenin disposition to differences in the bile acid profile and Fibroscan Fibrosis Score of healthy subjects compared to patients with NASH.

Conditions

Non-alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Hepatic exposure (AUC0→∞)

  Area under the hepatic concentration-time curve

  0-180 minutes

Secondary Outcomes (6)

• Systemic exposure (AUC0 →∞)

  0-300 minutes

• Cmax (hepatic)

  0-180 minutes

• Tmax (hepatic)

  0-180 minutes

• Xurine

  0-180 minutes

• CLuptake

  0-180 minutes

Study Arms (2)

Patients with NASH

EXPERIMENTAL

Each subject will be injected with \~2.5 mCi of Technetium Tc 99M Mebrofenin

Drug: Technetium Tc 99M Mebrofenin

Healthy Normal Volunteers

ACTIVE COMPARATOR

Each subject will be injected with \~2.5 mCi of Technetium Tc 99M Mebrofenin

Drug: Technetium Tc 99M Mebrofenin

Interventions

Technetium Tc 99M Mebrofenin DRUG

Each subject will be injected with \~2.5 mCi of Technetium Tc 99M Mebrofenin

Also known as: Choletec

Healthy Normal Volunteers; Patients with NASH

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects: defined as being free from significant cardiac, pulmonary, gastrointestinal, hepatic, biliary, renal, hematological, neurological and psychiatric disease as determined by history, physical examination and clinical laboratory test results.
• NASH subjects only: defined as those who have had a recent liver biopsy consistent with NASH without cirrhosis; NAS score \>3.
• Fluent and literate in English.
• Willing and able to give informed consent prior to entering the study.

You may not qualify if:

• Donation of blood within last 30 days.
• History of significant alcohol abuse (\>20g/day) and/or illicit drug use, whether successfully treated or not.
• Inability to abstain from alcohol for 48 hours prior to study visits.
• Inability to fast for 8 hours prior to study sample collection.
• Women who are pregnant, trying to become pregnant, or breast feeding.
• Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens at doses greater than those used for hormone replacement or valproate/valproic acid
• Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
• Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
• Serum blood glucose reading at study enrollment of \>200 mg/dL.
• Current use of antioxidants such as silymarin, vitamin C, glutathione, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin and vitamin E at standard doses will be allowed.
• Previous liver biopsy that demonstrated presence of cirrhosis.
• Radiologic imaging consistent with cirrhosis or portal hypertension.
• Evidence of decompensated liver disease defined as any of the following: serum albumin \<3.2 g/dL, total bilirubin \> 1.5 mg/dL, or PT/INR \> 1.3 times normal at screening, or history or presence of ascites, encephalopathy, or bleeding from esophageal varices.
• Serum creatinine of 2.0 mg/dL or greater, or on dialysis, at screening.
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers (bile acids or inflammation).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

UNC Hospitals

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (1)

• Pfeifer ND, Goss SL, Swift B, Ghibellini G, Ivanovic M, Heizer WD, Gangarosa LM, Brouwer KL. Effect of Ritonavir on (99m)Technetium-Mebrofenin Disposition in Humans: A Semi-PBPK Modeling and In Vitro Approach to Predict Transporter-Mediated DDIs. CPT Pharmacometrics Syst Pharmacol. 2013 Jan 2;2(1):e20. doi: 10.1038/psp.2012.21.

  PMID: 23887590 RESULT

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

technetium Tc 99m mebrofenin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Sidney Barritt, M.D., MSCR

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Jason R. Slizgi, B.S.

  UNC School of Pharmacy

  STUDY DIRECTOR

• Kim Brouwer, PharmD, PhD

  UNC School of Pharmacy

  STUDY DIRECTOR

• Josh Kaullen, Pharm.D.

  UNC School of Pharmacy

  STUDY DIRECTOR

• Marijia Ivanovic, Ph.D.

  UNC Department of Radiology

  STUDY DIRECTOR

• Paul Stewart, Ph.D.

  UNC School of Public Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2014
• First Posted: September 9, 2014
• Study Start: April 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 5, 2017

Record last verified: 2017-05

Locations

US (1)