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Class 3 Biowaivers

This study has been completed.
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
University of Maryland Identifier:
First received: November 9, 2009
Last updated: November 21, 2013
Last verified: December 2010

The Biopharmaceutics Classification System (BCS) is employed by the US FDA to categorize drug substances into 4 classes and to characterize drugs in terms of aqueous solubility and intestinal permeability. The four BCS categories for a drug substance are Class 1, Class 2, Class 3, and Class 4. Biopharmaceutical properties of aqueous solubility and intestinal permeability with drug product dissolution determine the rate and extent of drug absorption from immediate-release (IR) and solid oral dosages forms (e.g. tablets,capsules). Each class exhibits information regarding biopharmaceutic properties and bioequivalence. For example, Class 1 drugs have the most favorable oral biopharmaceutic properties (high solubility and high permeability). With these biopharmaceutic properties for class 1 drugs, results in vivo bioequivalence (BE) studies for rapidly dissolving IR solid oral dosage forms the FDA provided waivers. This approach alone has resulted in new and generic drugs approved based on vitro data alone (i.e. biowaived), with great savings in resources and reduction in unnecessary human testing.

Objectives: 1) The primary objective of this study is to assess whether common excipients cause bioinequivalence of Class 3 drugs. 2) The secondary objective is the results of the study will contribute towards providing scientific evidence to the FDA for consideration of Class 3 drugs for BCS-based biowaivers.

Hypotheses: The investigators anticipate that common excipients do not cause bioinequivalence. 1) Hence, the hypothesize of this study is commonly used excipients in oral medications (tablets, capsules) modulate the rate or extent of Class 3 drug absorption and result in bioinequivalence. 2) Alternative hypothesis is that commonly used excipients in oral medications (tablets, capsules) do not modulate the rate or extent of Class 3 drug absorption and do not result in bioinequivalence.

Condition Intervention Phase
Drug: cimetidine (or acyclovir)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Evaluation of Biopharmaceutics Classification System Class 3 Drugs for Possible Biowaivers

Resource links provided by NLM:

Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Change in the amount of drug in blood during the study [ Time Frame: 10 hours ]
    Plasma samples will be collected to measure level of drug

Enrollment: 48
Study Start Date: June 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cimetidine (or acyclovir) capsule 1
formulation 1
Drug: cimetidine (or acyclovir)
cimetidine (or acyclovir) 200mg (single dose)
Experimental: cimetidine (or acyclovir) capsule 2
formulation 2
Drug: cimetidine (or acyclovir)
cimetidine (or acyclovir) 200mg (single dose)
Experimental: cimetidine (or acyclovir) capsule 3
formulation 3
Drug: cimetidine (or acyclovir)
cimetidine (or acyclovir) 200mg (single dose)
Active Comparator: cimetidine (or acyclovir) reference
reference product
Drug: cimetidine (or acyclovir)
cimetidine (or acyclovir) 200mg (single dose)


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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 OTC 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 GI function
  • Currently taking cimetidine (or acyclovir) or medication known to interact with cimetidine (or acyclovir)
  • Allergic to cimetidine (or acyclovir)
  • 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.
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Please refer to this study by its identifier: NCT01010698

United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Food and Drug Administration (FDA)
Principal Investigator: James Polli University of Maryland
  More Information

Responsible Party: University of Maryland Identifier: NCT01010698     History of Changes
Other Study ID Numbers: HP-00044278
HSF223200810041C ( Other Grant/Funding Number: Food and Drug Administration )
Study First Received: November 9, 2009
Last Updated: November 21, 2013

Keywords provided by University of Maryland:

Additional relevant MeSH terms:
Anti-Ulcer Agents
Gastrointestinal Agents
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents processed this record on April 26, 2017