Class 3 Biowaivers

Evaluation of Biopharmaceutics Classification System Class 3 Drugs for Possible Biowaivers

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: cimetidine (or acyclovir)

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 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 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.

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: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the amount of drug in blood during the study	Plasma samples will be collected to measure level of drug	10 hours

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: November 9, 2009
• First Submitted That Met QC Criteria: November 9, 2009
• First Posted (Estimate): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): November 6, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; excipient; cimetidine; formulation; acyclovir
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Acyclovir; Cimetidine
• Other Study ID Numbers: HP-00044278; HSF223200810041C (Other Grant/Funding Number: Food and Drug Administration)