Cimetidine Biowaivers

Evaluation of Excipient Effects on Biopharmaceuticals Classification System (BCS) Class 3 Drug Cimetidine

The purpose of this research is to see if non-drug ingredients in capsules and oral solutions affect how well drugs are absorbed. This is called "bioequivalence." Medications taken by mouth, such as capsules and solutions, need to be absorbed into the body in order to do any good. Capsules and solutions contain a drug, but also contain non-drug ingredients that are called excipients or fillers. Excipients in the capsules and solutions can impact how much drug is absorbed into the body. This is called "bioINequivalence." Capsules and solutions in this research contain the drug cimetidine. This drug is being used since it has high water solubility (can dissolve in water) and low ability to be absorbed.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Drug: cimetidine

Detailed Description

The investigators anticipate that common excipients do not cause bioINequivalence. 1) The hypothesize is that commonly used excipients in oral medications change the rate or extent of Class 3 drug absorption and result in bioINequivalence. 2) Alternative hypothesis is that commonly used excipients in oral medications do not change the rate or extent of Class 3 drug absorption and do not result in bioINequivalence.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female
• Age 18-55
• Healthy volunteers: Subjects in good health, as determined by screening evaluation that is not greater than 30 days before the first drug study visit
• Willing to avoid caffeine containing products 24 hours prior to and day of study visits
• Willing to stop all over the counter medications for 24 hours prior to and during study visits
• Able to provide informed consent

Exclusion Criteria:

• Presence of significant medical disease (including cardiovascular, pulmonary, hematologic, endocrine, immunologic, neurologic, gastrointestinal or psychiatric)
• Presence of hepatic, renal disease
• Pregnant women, breast feeding or trying to become pregnant
• Excessive alcohol use (i.e. current physical, behavioral, or personal manifestations related to the abuse or dependency on alcohol)
• Routine use (i.e. daily or weekly) prescription medication except birth control pills
• Routine use (i.e. daily or weekly) use of acid blockers, antacids, anti-diarrhea, stimulants, appetite suppressants, or anti nausea medication or other drugs that modulate gastrointestinal function
• Currently taking cimetidine or medication known to interact with cimetidine
• Allergic to cimetidine
• Undergoing therapy for solid tumor or blood malignancy
• Any condition in which in the opinion of the PI or medical physician would increase risk to the subject or interfere with the integrity of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CimTest-A; 200mg cimetidine (as 2 capsules)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Experimental: CimTest-B; 200mg cimetidine (as 2 capsules)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Active Comparator: Sorbitol-free cimetidine solution; 200mg cimetidine (as oral liquid)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Experimental: Commercial cimetidine solution; 200mg cimetidine (as oral liquid)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	pharmacokinetic exposure (ng*hr/ml)	0-10 hours

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: James Polli, PhD, University of Maryland, Baltimore

Publications and helpful links

General Publications

• Rege BD, Yu LX, Hussain AS, Polli JE. Effect of common excipients on Caco-2 transport of low-permeability drugs. J Pharm Sci. 2001 Nov;90(11):1776-86. doi: 10.1002/jps.1127.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: December 7, 2010
• First Posted (Estimate): December 9, 2010

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: pharmacokinetics; cimetidine; formulation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Cimetidine
• Other Study ID Numbers: HP-00046139; HHSF2232000910020C (Other Grant/Funding Number: HHSF2232000910020C)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No