Healthy
Conditions
Keywords
cimetidine, pharmacokinetics, formulation
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.
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.
Interventions
DRUGDrug: cimetidine
cimetidine 200mg total dose (single dose) as either CimTest-A capsules, CimTest-B capsules, sorbitol-free solution, or commercial cimetidine solution
Sponsors
Food and Drug Administration (FDA)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC | 0-10 hours | pharmacokinetic exposure (ng\*hr/ml) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cimetidine cimetidine 200mg total dose (single dose) | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cimetidine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 1 / 25 | 0 / 24 | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
AUC
pharmacokinetic exposure (ng\*hr/ml)
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: CimTest-A | AUC | 3896 ng*hr/ml | Standard Error 181 |
| Experimental: CimTest-B | AUC | 3661 ng*hr/ml | Standard Error 186 |
| Active Comparator: Sorbitol-free Cimetidine Solution | AUC | 3495 ng*hr/ml | Standard Error 183 |
| Experimental: Commercial Cimetidine Solution | AUC | 3512 ng*hr/ml | Standard Error 193 |