Central Nervous System Effects Following Infusion of Diphenhydramine Using Pharmacokinetic and Pharmacodynamic Modeling

Study Overview
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Brief Summary
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This study seeks to explore the magnitude and duration of central nervous system effects and pharmacokinetics after intravenous infusion of diphenhydramine.

Official Title
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The Magnitude and Duration of the Central Nervous System Effects Following Intravenous Infusion of Diphenhydramine Using Pharmacokinetic and Pharmacodynamic Modeling

Conditions
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Central Nervous System Effects of Diphenhydramine, Pharmacokinetics of Diphenhydramine

Intervention / Treatment
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* Drug: DiphenhydrAMINE Injectable Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically-stable volunteers of either gender between 35 and 50 years old or over the age of 65 No medication changes anticipated for the duration of the study except as defined in protocol Exclusion Criteria: Insulin-dependent diabetes Psychiatric or neurologic disease affecting cognition in a way that may interfere with study outcomes in the opinion of the investigator Unstable Coronary Artery Disease (active angina, MI within 6 months, stent placement within 6 months, cardiac surgery within 6 months) Estimated CrCl < 30 mL/min using the Cockroft-Gault equation based on ideal body weight or total body weight Any malignancy actively being treated or not in remission Currently taking any CNS stimulant or depressant medications that may interfere with study outcomes in the opinion of the investigator unless using as defined in the protocol Positive toxicology test for marijuana at screening visit or visit 2 or using marijuana not as defined in the protocol Active or recent history of a substance use disorder within one year Any medical condition that in the opinion of the investigator would disqualify the subject from participation in the study Female subjects who are pregnant, planning to become pregnant, or breastfeeding on any study day Female subjects of childbearing potential unwilling to use acceptable method of contraception during the study as defined in the protocol Contraindication, known allergy, or suspected intolerability to study medication Receipt of an antihistamine within 5 half-lives prior to the start of study visit 1 or study visit 2, as determined by the investigator Positive toxicology test for a drug that is inconsistent with permitted medication use (defined in the protocol) as interpreted by the investigator Participation in any other investigational drug study during the study or within 4 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: DiphenhydrAMINE Injectable Solution|Intravenous infusion of diphenhydramine 50 mg.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score of battery of cognitive function tests | Change in the results of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation after diphenhydramine administration compared to baseline | Change from before to after diphenhydramine administration (30, 60, 210, 240, 450, and 480 minutes after diphenhydramine) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elderly vs. adult score of battery of cognitive function tests at specified time points | Score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (0, 30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | Before and after diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) | 
| Elderly vs. adult diphenhydramine AUC | Difference between diphenhydramine pharmacokinetic area under the curve (AUC) in elderly subjects aged 65+ vs. adult subjects aged 35 to 50 | Immediately after diphenhydramine administration to 480 minutes after diphenhydramine administration | 
| Elderly vs. adult change in score of battery of cognitive function tests after diphenhydramine | Change in the score of the CANTAB battery of cognitive function tests (reaction time, rapid visual information processing, paired associates learning, spatial working memory, digit span) and visual analog scale for sedation in elderly subjects aged 65+ compared to adult subjects aged 35 to 50 at specified time points (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) compared to baseline. | After diphenhydramine administration (30, 60, 210, 240, 450, 480 minutes after diphenhydramine administration) |