Clinical trial

Single-Dose Pharmacokinetics of Atropine Oral Gel in Healthy Adults

Name

144918

Description

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

Trial arms

Trial start

2022-10-01

Estimated PCD

2023-06-30

Trial end

2024-07-01

Status

Active (not recruiting)

Phase

Early phase I

Treatment

Atropine sulfate gel (0.01%)

A research nurse will measure 1 gram of gel using a calibrated measuring spoon and will provide it to the participant for self-administration.

Arms:

0.1 mg of atropine

Other names:

Atropine gel, mucoadhesive atropine gel

Size

Primary endpoint

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.

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.

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.

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.

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.

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.

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['EARLY_PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ESTIMATED'}}

Updated at

2023-11-22

1 organization

1 product

2 indications

Organization

Product

Indication

Indication