Impact of Formulation on Ciprofloxacin Oral Absorption - Full Text View

Sponsor:	University of Maryland
Collaborator:	Food and Drug Administration (FDA)
Information provided by:	University of Maryland
ClinicalTrials.gov Identifier:	NCT00992329

Purpose

The purpose of this research is to see if certain tablet formulation factors affect oral drug absorption. Medications taken by mouth, such as tablets, need to be absorbed into the body in order to do any good. Tablets contain a drug, but also contain non-drug ingredients that are called excipients or fillers. Excipients in the tablet, and the way in which the tablet is manufactured, both can impact how much drug is absorbed into the body. That is, tablet formulation factors can cause a tablet to be effective or not effective.

Tablets in this research contain the drug ciprofloxacin hydrochloride. Ciprofloxacin is an antibiotic to treat infections, such as lung infections. This drug is being used since it has low water solubility and is probably sensitive to tablet formulation factors.

Condition	Intervention	Phase
Healthy	Drug: ciprofloxacin	Phase I

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:	Impact of Formulation on Ciprofloxacin Oral Absorption

Resource links provided by NLM:

Drug Information available for: Ciprofloxacin Ciprofloxacin hydrochloride Ciprofloxacin lactate

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Amount of ciprofloxacin absorbed [ Time Frame: 10 hours ] [ Designated as safety issue: No ]
Blood samples will be collected to measure level of ciprofloxacin.

Secondary Outcome Measures:

Difference between humans and dogs in the amount of cipro absorbed. [ Time Frame: 10 hours ] [ Designated as safety issue: No ]
Blood samples will be collected to measure level of ciprofloxacin.

Estimated Enrollment:	16
Study Start Date:	December 2009
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ciprofloxacin tab1 formulation 1	Drug: ciprofloxacin ciprofloxacin 200mg tablet (single dose)
Experimental: ciprofloxacin tab2 formulation 2	Drug: ciprofloxacin ciprofloxacin 200mg tablet (single dose)
Experimental: ciprofloxacin tab 3 formulation 3	Drug: ciprofloxacin ciprofloxacin 200mg tablet (single dose)
Active Comparator: ciprofloxacin reference reference product	Drug: ciprofloxacin ciprofloxacin 200mg tablet (single dose)

Detailed Description:

Dogs and humans exhibit differences in gastrointestinal physiology. The development of pharmaceuticals for both humans and dogs typically depends upon pharmacokinetic studies in the other species. Product design and quality attributes for dogs (and for humans)generally conduct such extrapolations in a simplistic fashion, without a systematic account of the differential intestinal physiology between dog and human. This project aims to elucidate product quality differences between human and dog oral solid dosage forms as a result of the differential physiology between the two specifies. This insight will facilitate the regulation of canine medicines by highlighting how product standards for human medicines are either too liberal or too restrictive for canine medicines.

Ciprofloxacin hydrochloride will be used as a model poorly soluble drug. A range of immediate-release (IR) tablets will be formulated to map the design space. Formulations will be fast, medium, and slow, with respect to dissolution rate of drug. Ciprofloxacin is expected to exhibit formulation-dependent pharmacokinetics, which is additionally impacted by the differential physiology between dog and humans. In particular, the investigators anticipate a greater sensitivity to formulation for dogs than for humans. Consequently, the investigators anticipate dogs to be more sensitive to formulations, where such critical formulation factors must be considered in canine product design and regulation.

Objectives: 1) The primary objective of this human study is to assess whether specific formulation factors impact the rate and extent of ciprofloxacin oral absorption, as well as the absolute absorption profile of ciprofloxacin. 2) The secondary objective is to assess if dogs exhibit a greater sensitivity to formulation than do humans.

Hypotheses: The investigators anticipate that humans exhibit a modest sensitivity to specific tablet formulation factors. 1) Hence, the hypothesis of this human study is that humans do not exhibit a sensitivity to specific formulation factors and show no in vitro - in vivo correlation to dissolution rate. 2) Alternative hypothesis is that humans do exhibit a sensitivity to specific formulation factors and show an in vitro - in vivo correlation to dissolution rate.

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 ciprofloxacin or tizanidine
Allergic to ciprofloxacin or any quinolone-type antibiotic (e.g. levofloxacin)
Currently taking a corticosteroid drug (e.g. prednisone)
Had a kidney, heart, or lung transplant
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992329

Contacts

Contact: James Polli

410-706-8292

jpolli@rx.umaryland.edu

Locations

United States, Maryland
University of Maryland	Recruiting
Baltimore, Maryland, United States, 21201
Contact: James Polli 410-706-8292 jpolli@rx.umaryland.edu
Principal Investigator: James Polli

Sponsors and Collaborators

University of Maryland

Food and Drug Administration (FDA)

Investigators

Principal Investigator:

James Polli

University of Maryland

More Information

Publications:

Polli JE, Rekhi GS, Augsburger LL, Shah VP. Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets. J Pharm Sci. 1997 Jun;86(6):690-700.

Responsible Party:	James E Polli, University of Maryland
ClinicalTrials.gov Identifier:	NCT00992329 History of Changes
Other Study ID Numbers:	HP-00043432, HHSF223200810030C
Study First Received:	October 2, 2009
Last Updated:	November 22, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Maryland:

ciprofloxacin
pharmacokinetics
formulation

Additional relevant MeSH terms:

Ciprofloxacin
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012