Cimetidine Biowaivers

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT01256879
• Collaborator: Food and Drug Administration (FDA) (U.S. Fed)
• Enrollment: 25
• Location: 1
• Arms: 4
• Duration (Months): 38
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this research is to see if non-drug ingredients in capsules and oral solutions affect how well drugs are absorbed. This is called "bioequivalence." Medications taken by mouth, such as capsules and solutions, need to be absorbed into the body in order to do any good. Capsules and solutions contain a drug, but also contain non-drug ingredients that are called excipients or fillers. Excipients in the capsules and solutions can impact how much drug is absorbed into the body. This is called "bioINequivalence." Capsules and solutions in this research contain the drug cimetidine. This drug is being used since it has high water solubility (can dissolve in water) and low ability to be absorbed.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Drug: cimetidine	Phase 4

Detailed Description

The investigators anticipate that common excipients do not cause bioINequivalence. 1) The hypothesize is that commonly used excipients in oral medications change the rate or extent of Class 3 drug absorption and result in bioINequivalence. 2) Alternative hypothesis is that commonly used excipients in oral medications do not change the rate or extent of Class 3 drug absorption and do not result in bioINequivalence.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Evaluation of Excipient Effects on Biopharmaceuticals Classification System (BCS) Class 3 Drug Cimetidine
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CimTest-A 200mg cimetidine (as 2 capsules)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Experimental: CimTest-B 200mg cimetidine (as 2 capsules)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Active Comparator: Sorbitol-free cimetidine solution 200mg cimetidine (as oral liquid)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet
Experimental: Commercial cimetidine solution 200mg cimetidine (as oral liquid)	Drug: Drug: cimetidine; cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution; Other Names: Tagamet

Outcome Measures

Primary Outcome Measures

1. AUC [0-10 hours]

   pharmacokinetic exposure (ng*hr/ml)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• 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 over the counter 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 gastrointestinal function

• Currently taking cimetidine or medication known to interact with cimetidine

• Allergic to cimetidine

• 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

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• Food and Drug Administration (FDA)

Investigators

• Principal Investigator: James Polli, PhD, University of Maryland, Baltimore

Study Documents (Full-Text)

None provided.

More Information

Publications

• Rege BD, Yu LX, Hussain AS, Polli JE. Effect of common excipients on Caco-2 transport of low-permeability drugs. J Pharm Sci. 2001 Nov;90(11):1776-86.

• Responsible Party: James E Polli, Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT01256879
• Other Study ID Numbers: HP-00046139; HHSF2232000910020C
• First Posted: Dec 9, 2010
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by James E Polli, Professor, University of Maryland, Baltimore: cimetidine; pharmacokinetics; formulation
• Additional relevant MeSH terms: Cimetidine

Study Results

Participant Flow

Arm/Group Title	Cimetidine
Arm/Group Description	cimetidine 200mg total dose (single dose)
Period Title: Overall Study
STARTED	25
CimTest-A	25
CimTest-B	24
Sorbitol-free Cimetidine Solution	24
Commercial Cimetidine Solution	24
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Cimetidine
Arm/Group Description	cimetidine 200mg total dose (single dose)
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	15 60%
Male	10 40%

Outcome Measures

1. Primary Outcome

Title	AUC
Description	pharmacokinetic exposure (ng*hr/ml)
Time Frame	0-10 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental: CimTest-A	Experimental: CimTest-B	Active Comparator: Sorbitol-free Cimetidine Solution	Experimental: Commercial Cimetidine Solution
Arm/Group Description	cimetidine capsule with hydroxypropyl methylcellulose (HPMC), a type of filler cimetidine: cimetidine 200mg total dose (single dose)	cimetidine capsule with magnesium stearate, a type of filler cimetidine: cimetidine 200mg total dose (single dose)	non-commercial cimetidine solution cimetidine: cimetidine 200mg total dose (single dose)	commercial cimetidine solution cimetidine: cimetidine 200mg total dose (single dose)
Measure Participants	24	24	24	24
Mean (Standard Error) [ng*hr/ml]	3896 (181)	3661 (186)	3495 (183)	3512 (193)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental: CimTest-A, Experimental: CimTest-B, Experimental: Commercial Cimetidine Solution
	Comments
	Type of Statistical Test	Other
	Comments	Each CimTest-A, CimTest-B, and Commercial Cimetidine Solution are compared to Active Comparator (i.e. Sorbitol-free Cimetidine Solution), as a percentage of Active Comparator, per routine FDA bioequivalence testing of AUC.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Bioequivalence testing of AUC, per FDA guidance, is applied. Each CimTest-A, CimTest-B, and Commercial Cimetidine Solution are compared to Active Comparator (i.e. Sorbitol-free Cimetidine Solution), as a percentage of Active Comparator, per routine FDA bioequivalence testing of AUC. The upper and lower 90% Confidence Interval for CimTest-A is 104.4% to 120.6%. The upper and lower 90% Confidence Interval for CimTest-B is 97.9% to 113.0%. The upper and lower 90% Confidence Interval for Commercial Cimetidine Solution is 93.2% to 107.7%.

Adverse Events

Time Frame	10 hours
Arm/Group Title	Experimental: CimTest-A		Experimental: CimTest-B		Active Comparator: Sorbitol-free Cimetidine Solution		Experimental: Commercial Cimetidine Solution
Arm/Group Description	cimetidine capsule with hydroxypropyl methylcellulose (HPMC), a type of filler cimetidine: cimetidine 200mg total dose (single dose)		cimetidine capsule with magnesium stearate, a type of filler cimetidine: cimetidine 200mg total dose (single dose)		non-commercial cimetidine solution cimetidine: cimetidine 200mg total dose (single dose)		commercial cimetidine solution cimetidine: cimetidine 200mg total dose (single dose)
All Cause Mortality
	Experimental: CimTest-A		Experimental: CimTest-B		Active Comparator: Sorbitol-free Cimetidine Solution		Experimental: Commercial Cimetidine Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Experimental: CimTest-A		Experimental: CimTest-B		Active Comparator: Sorbitol-free Cimetidine Solution		Experimental: Commercial Cimetidine Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Experimental: CimTest-A		Experimental: CimTest-B		Active Comparator: Sorbitol-free Cimetidine Solution		Experimental: Commercial Cimetidine Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/25 (4%)		0/24 (0%)		0/24 (0%)		0/24 (0%)
Skin and subcutaneous tissue disorders
pain	1/25 (4%)	1	0/24 (0%)	0	0/24 (0%)	0	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.