Pharmacokinetics of Atropine Oral Gel

NCT05164367 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 144918
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cerebral Palsy; Sialorrhea

Keywords

Pharmacokinetics; Cerebral Palsy; Sialorrhea; Atropine sulfate gel

Outcome Measures

Primary Outcomes (5)

• 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.

Study Arms (1)

0.1 mg of atropine

EXPERIMENTAL

1 gram of gel by topical application in the oral cavity once.

Drug: Atropine sulfate gel (0.01%)

Interventions

Atropine sulfate gel (0.01%) DRUG

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

Also known as: Atropine gel, mucoadhesive atropine gel

0.1 mg of atropine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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. \[ULN for AST = 40 U/L, ULN for ALT = 60 U/L\]

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (23)

• Reid SM, Westbury C, Chong D, Johnstone BR, Guzys A, Reddihough DS. Long-term impact of saliva control surgery in children with disability. J Plast Reconstr Aesthet Surg. 2019 Jul;72(7):1193-1197. doi: 10.1016/j.bjps.2019.02.020. Epub 2019 Mar 2.

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• Speyer R, Cordier R, Kim JH, Cocks N, Michou E, Wilkes-Gillan S. Prevalence of drooling, swallowing, and feeding problems in cerebral palsy across the lifespan: a systematic review and meta-analyses. Dev Med Child Neurol. 2019 Nov;61(11):1249-1258. doi: 10.1111/dmcn.14316. Epub 2019 Jul 22.

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• Parkes J, Hill N, Platt MJ, Donnelly C. Oromotor dysfunction and communication impairments in children with cerebral palsy: a register study. Dev Med Child Neurol. 2010 Dec;52(12):1113-9. doi: 10.1111/j.1469-8749.2010.03765.x. Epub 2010 Aug 31.

  PMID: 20813020 BACKGROUND

• Reid SM, McCutcheon J, Reddihough DS, Johnson H. Prevalence and predictors of drooling in 7- to 14-year-old children with cerebral palsy: a population study. Dev Med Child Neurol. 2012 Nov;54(11):1032-6. doi: 10.1111/j.1469-8749.2012.04382.x. Epub 2012 Aug 9.

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• Reid SM, Westbury C, Guzys AT, Reddihough DS. Anticholinergic medications for reducing drooling in children with developmental disability. Dev Med Child Neurol. 2020 Mar;62(3):346-353. doi: 10.1111/dmcn.14350. Epub 2019 Sep 8.

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• Norderyd J, Graf J, Marcusson A, Nilsson K, Sjostrand E, Steinwall G, Arleskog E, Bagesund M. Sublingual administration of atropine eyedrops in children with excessive drooling - a pilot study. Int J Paediatr Dent. 2017 Jan;27(1):22-29. doi: 10.1111/ipd.12219. Epub 2015 Dec 27.

  PMID: 26708211 BACKGROUND

• Protus BM, Grauer PA, Kimbrel JM. Evaluation of atropine 1% ophthalmic solution administered sublingually for the management of terminal respiratory secretions. Am J Hosp Palliat Care. 2013 Jun;30(4):388-92. doi: 10.1177/1049909112453641. Epub 2012 Jul 24.

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• De Simone GG, Eisenchlas JH, Junin M, Pereyra F, Brizuela R. Atropine drops for drooling: a randomized controlled trial. Palliat Med. 2006 Oct;20(7):665-71. doi: 10.1177/0269216306071702.

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• Lawrence R, Bateman N. Surgical Management of the Drooling Child. Curr Otorhinolaryngol Rep. 2018;6(1):99-106. doi: 10.1007/s40136-018-0188-2. Epub 2018 Mar 20.

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• Leung JG, Schak KM. Potential problems surrounding the use of sublingually administered ophthalmic atropine for sialorrhea. Schizophr Res. 2017 Jul;185:202-203. doi: 10.1016/j.schres.2016.12.028. Epub 2016 Dec 30. No abstract available.

  PMID: 28043733 BACKGROUND

• Singla AK, Chawla M, Singh A. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Dev Ind Pharm. 2000 Sep;26(9):913-24. doi: 10.1081/ddc-100101318.

  PMID: 10914315 BACKGROUND

• Keegan G, Smart J, Ingram M, Barnes L, Rees G, Burnett G. An in vitro assessment of bioadhesive zinc/carbomer complexes for antimicrobial therapy within the oral cavity. Int J Pharm. 2007 Aug 1;340(1-2):92-6. doi: 10.1016/j.ijpharm.2007.03.023. Epub 2007 Mar 24.

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• Kelly HM, Deasy PB, Busquet M, Torrance AA. Bioadhesive, rheological, lubricant and other aspects of an oral gel formulation intended for the treatment of xerostomia. Int J Pharm. 2004 Jul 8;278(2):391-406. doi: 10.1016/j.ijpharm.2004.03.022.

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• Allison RR, Ambrad AA, Arshoun Y, Carmel RJ, Ciuba DF, Feldman E, Finkelstein SE, Gandhavadi R, Heron DE, Lane SC, Longo JM, Meakin C, Papadopoulos D, Pruitt DE, Steinbrenner LM, Taylor MA, Wisbeck WM, Yuh GE, Nowotnik DP, Sonis ST. Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck. Cancer. 2014 May 1;120(9):1433-40. doi: 10.1002/cncr.28553.

  PMID: 24877167 BACKGROUND

• Alcon (2018). Viscotears® Liquid Gel [carbomer (polyacrylic acid)] - Patient Information Leaflet

  BACKGROUND

• Regulatory Information for Carbopol®* 971P NF Polymer & Carbopol® 71G NF Polymer. file:///C:/Users/u0840209/Downloads/TDS-328_Carbopol_971P_71G_Regulatory_PH_Version%20(1).pdf

  BACKGROUND

• Zeller RS, Lee HM, Cavanaugh PF, Davidson J. Randomized Phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. Ther Clin Risk Manag. 2012;8:15-23. doi: 10.2147/TCRM.S26893. Epub 2012 Jan 25.

  PMID: 22298950 BACKGROUND

• Reid SM, Johnson HM, Reddihough DS. The Drooling Impact Scale: a measure of the impact of drooling in children with developmental disabilities. Dev Med Child Neurol. 2010 Feb;52(2):e23-8. doi: 10.1111/j.1469-8749.2009.03519.x. Epub 2009 Oct 15.

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• Jones JM, Watkins CA, Hand JS, Warren JJ, Cowen HJ. Comparison of three salivary flow rate assessment methods in an elderly population. Community Dent Oral Epidemiol. 2000 Jun;28(3):177-84. doi: 10.1034/j.1600-0528.2000.280303.x.

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• Dias BLS, Fernandes AR, Maia HS Filho. Treatment of drooling with sublingual atropine sulfate in children and adolescents with cerebral palsy. Arq Neuropsiquiatr. 2017 May;75(5):282-287. doi: 10.1590/0004-282X20170033.

  PMID: 28591387 BACKGROUND

• Azapagasi E, Kendirli T, Perk O, Kutluk G, Oz Tuncer G, Teber S, Cobanoglu N. Sublingual Atropine Sulfate Use for Sialorrhea in Pediatric Patients. J Pediatr Intensive Care. 2020 Sep;9(3):196-200. doi: 10.1055/s-0040-1708552. Epub 2020 Apr 7.

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• Rapoport A. Sublingual atropine drops for the treatment of pediatric sialorrhea. J Pain Symptom Manage. 2010 Nov;40(5):783-8. doi: 10.1016/j.jpainsymman.2010.02.007. Epub 2010 Jun 11.

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Related Links

• Prescribing information of Cuvposa-glycopyrrolate liquid.

MeSH Terms

Conditions

Cerebral Palsy; Sialorrhea

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Venkata K. Yellepeddi, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 20, 2021
• Study Start: October 1, 2022
• Primary Completion: June 30, 2023
• Study Completion: December 10, 2024
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)