Impact of Formulation on Ciprofloxacin Oral Absorption

This study has been completed.
Sponsor:
Collaborator:
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
University of Maryland
ClinicalTrials.gov Identifier:
NCT00992329
First received: October 2, 2009
Last updated: November 21, 2013
Last verified: November 2013
  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 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: Impact of Formulation on Ciprofloxacin Oral Absorption

Resource links provided by NLM:


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.


Enrollment: 16
Study Start Date: January 2013
Study Completion Date: November 2013
Primary Completion Date: November 2013 (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
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: NCT00992329

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

Publications:
Responsible Party: 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 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
ciprofloxacin
pharmacokinetics
formulation

Additional relevant MeSH terms:
Ciprofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 11, 2014