Clinical trial NCT05164367: Pharmacokinetics of Atropine Oral Gel
Official title: Single-Dose Pharmacokinetics of Atropine Oral Gel in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cerebral Palsy
Sialorrhea
Keywords: Pharmacokinetics
Cerebral Palsy
Sialorrhea
Atropine sulfate gel
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2021-12-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent and authorization.
2. Study participants must be able to complete consent, and all study evaluations written in the English language.

Exclusion Criteria:

1. Female subjects who are pregnant or nursing at the time of screening
2. Chemotherapy or radiotherapy treatment within the last three months
3. 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,
   1. k=0.7 if female
   2. k=0.9 if male
   3. α=-0.329 if female
   4. α=-0.411 if male
   5. min=The minimum of Scr/k or 1
   6. max=The maximum of Scr/k or 1
   7. Scr = serum creatinine (mg/dL)
4. 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:

   1. Bilirubin \> 3 x upper limit of normal (ULN). \[ULN for bilirubin = 1.4 mg/dL\]
   2. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \> 3 x ULN values used by the laboratory performing the test. \[ULN for AST = 40 U/L, ULN for ALT = 60 U/L\]
   3. Alkaline phosphatase (ALP) \> 3 x ULN \[ULN for ALP = 126 U/L)
5. Deforming lesions of the oral cavity
6. Previous head and/or neck radiotherapy
7. Patients with a history of hypersensitivity reaction towards atropine and/or Carbopol 980 NF or any carbomers
8. Patients with heart conditions such as congenital heart disease, heart failure, coronary heart disease, myocardial infarction, and arrhythmia
9. Patients with acute glaucoma that may be exacerbated with atropine administration.
10. Patients with partial pyloric stenosis or other diseases related to gastrointestinal obstruction.
11. Patients diagnosed with urinary retention
12. Treatment with any other investigational drug during the 30 days prior to enrollment into the study
13. Patients receiving anticholinergic medications at baseline.
14. Patients who are receiving immunosuppression
15. Patients who are actively being treated for an infection
16. Patients with a history of salivary gland obstruction or stones
17. Patients with a history of chronic lung disease or chronic obstructive pulmonary disease (COPD)
18. Patients with an artificial airway (tracheostomy)
19. Patient taking monoamine oxidase inhibitors

Primary outcomes:
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Venkata K. Yellepeddi, PhD
role: PRINCIPAL_INVESTIGATOR
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