Pharmacokinetics of Atropine Oral Gel

Study Overview
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Brief Summary
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To evaluate the single-dose pharmacokinetics of atropine gel formulation after topical administration in the oral cavity of healthy adults.

Detailed Description
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This study is a single-dose, single-center, open-label study of the pharmacokinetics of atropine gel (0.01% w/w) after topical oral administration in healthy adults. Study participants will be recruited by Drs. Murphy, Darro, and Yellepeddi at the Center for Clinical and Translation Science (CCTS), University of Utah. Participants who meet eligibility criteria will be recruited in the study after signing informed consent. Each of the 10 participants will receive 1 gram of atropine gel (0.01% w/w) containing 0.1 mg atropine via self-administration of gel into the oral cavity. Dr. Yellepeddi is a licensed pharmacist in the State of Utah and will train subjects in the administration of atropine gel in the oral cavity. A series of timed blood samples (0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours, 7 mL each time point) will be collected in commercial tubes, and plasma will be separated by centrifugation. The plasma samples will be stored frozen until further analysis by the Center for Human Toxicology (CHT), University of Utah.

Official Title
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Single-Dose Pharmacokinetics of Atropine Oral Gel in Healthy Adults

Conditions
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Cerebral Palsy, Sialorrhea

Intervention / Treatment
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* Drug: Atropine sulfate gel (0.01%)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent and authorization. Study participants must be able to complete consent, and all study evaluations written in the English language. Exclusion Criteria: Female subjects who are pregnant or nursing at the time of screening Chemotherapy or radiotherapy treatment within the last three months Severe renal impairment defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated using the CKD-EPI creatinine equation: eGFR (mL/min/1.73 m2) = 141 x min(Scr/k, 1)α x max(Scr/k,1)-1.209 x 0.993Age x 1.018 [if female] x 1.159 [if black] Where, k=0.7 if female k=0.9 if male α=-0.329 if female α=-0.411 if male min=The minimum of Scr/k or 1 max=The maximum of Scr/k or 1 Scr = serum creatinine (mg/dL) Acute hepatitis in the prior 6 months, a prior history of cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure; and/or any of the following blood test results, for any individual, when assessed for eligibility: Bilirubin > 3 x upper limit of normal (ULN). [ULN for bilirubin = 1.4 mg/dL] Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 3 x ULN values used by the laboratory performing the test. [ULN for AST = 40 U/L, ULN for ALT = 60 U/L] Alkaline phosphatase (ALP) > 3 x ULN [ULN for ALP = 126 U/L) Deforming lesions of the oral cavity Previous head and/or neck radiotherapy Patients with a history of hypersensitivity reaction towards atropine and/or Carbopol 980 NF or any carbomers Patients with heart conditions such as congenital heart disease, heart failure, coronary heart disease, myocardial infarction, and arrhythmia Patients with acute glaucoma that may be exacerbated with atropine administration. Patients with partial pyloric stenosis or other diseases related to gastrointestinal obstruction. Patients diagnosed with urinary retention Treatment with any other investigational drug during the 30 days prior to enrollment into the study Patients receiving anticholinergic medications at baseline. Patients who are receiving immunosuppression Patients who are actively being treated for an infection Patients with a history of salivary gland obstruction or stones Patients with a history of chronic lung disease or chronic obstructive pulmonary disease (COPD) Patients with an artificial airway (tracheostomy) Patient taking monoamine oxidase inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.1 mg of atropine<br>1 gram of gel by topical application in the oral cavity once. | Drug: Atropine sulfate gel (0.01%)<br>* A research nurse will measure 1 gram of gel using a calibrated measuring spoon and will provide it to the participant for self-administration.<br>* Other names: Atropine gel, mucoadhesive atropine gel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetic parameter time to reach maximum plasma concentration (Tmax) in healthy adults to see if atropine will reach detectable concentrations in plasma following topical oral administration in gel formulation. | Calculate the pharmacokinetic parameter Tmax after topical oral administration of 0.01% atropine gel. | The Tmax will be evaluated at timepoints 0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours after administration of gel to the oral cavity. | 
| Evaluate pharmacokinetic parameter time to reach maximum plasma concentration (Cmax) in healthy adults to see if atropine will reach detectable concentrations in plasma following topical oral administration in gel formulation. | Calculate the pharmacokinetic parameter Cmax after topical oral administration of atropine gel | The Cmax will be evaluated at timepoints 0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours after administration of gel to the oral cavity. | 
| Evaluate pharmacokinetic parameter area under the curve (AUC) in healthy adults to see if atropine will reach detectable concentrations in plasma following topical oral administration in gel formulation. | Calculate the pharmacokinetic parameter AUC after topical oral administration of atropine gel | The AUC will be evaluated at timepoints 0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours after administration of gel to the oral cavity. | 
| Evaluate pharmacokinetic parameter volume of distribution (Vd) in healthy adults to see if atropine will reach detectable concentrations in plasma following topical oral administration in gel formulation. | Calculate the pharmacokinetic parameter Vd after topical oral administration of atropine gel | The Vd will be evaluated at timepoints 0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours after administration of gel to the oral cavity. | 
| Evaluate pharmacokinetic parameter clearance (CL) in healthy adults to see if atropine will reach detectable concentrations in plasma following topical oral administration in gel formulation. | Calculate the pharmacokinetic parameter CL after topical oral administration of atropine gel | The CL will be evaluated at timepoints 0, 5, 10, 15, 30, 60 minutes, and 2, 4, 6, 8, and 24 hours after administration of gel to the oral cavity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Palsy, Pharmacokinetics, Sialorrhea, Atropine sulfate gel