Class 3 Biowaivers

This study has been completed.
Sponsor:
Collaborator:
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
University of Maryland
ClinicalTrials.gov Identifier:
NCT01010698
First received: November 9, 2009
Last updated: November 21, 2013
Last verified: December 2010
  Purpose

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
Healthy
Drug: cimetidine (or acyclovir)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
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 ] [ Designated as safety issue: No ]
    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)

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01010698

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

No publications provided

Responsible Party: University of Maryland
ClinicalTrials.gov Identifier: NCT01010698     History of Changes
Other Study ID Numbers: HP-00044278, HSF223200810041C
Study First Received: November 9, 2009
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
cimetidine
acyclovir
pharmacokinetics
excipient
formulation

Additional relevant MeSH terms:
Acyclovir
Cimetidine
Anti-Infective Agents
Anti-Ulcer Agents
Antiviral Agents
Enzyme Inhibitors
Gastrointestinal Agents
Histamine Agents
Histamine Antagonists
Histamine H2 Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014