Pharmacokinetics of Amiloride Nasal Spray in Healthy Volunteers

NCT ID: NCT04181008

Last Updated: 2023-03-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-28

Study Completion Date

2023-03-06

Brief Summary

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This study is a single-center, open-label study of the plasma pharmacokinetics of amiloride nasal spray at three different doses in healthy volunteers.

Detailed Description

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In this clinical study, we will evaluate the plasma pharmacokinetics of amiloride nasal spray in healthy volunteers at three different doses. The data obtained from this study will provide us with pharmacokinetic information that will help develop dosing regimens for future clinical efficacy studies in anxiety patients. Currently, there is no information on the bioavailability and pharmacokinetics of amiloride in humans after intranasal administration. All participants will be allowed to self-administer amiloride nasal spray at 0.2, 0.4, and 0.6 mg doses of amiloride. A series of timed blood samples (0,10, 15, 30, 60 minutes, and 4, 6, 8, 12 and 24 hours,1mL each time point) will be collected.

Primary objectives:

1. To evaluate the pharmacokinetics of amiloride nasal spray at three different doses 0.2, 0.4, and 0.6 mg in healthy human volunteers.
2. To calculate the following pharmacokinetic parameters after intranasal administration of amiloride: time to reach maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), area under the curve (AUC), the volume of distribution (Vd) and clearance (CL).

Conditions

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Pharmacokinetics

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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0.2 mg

Group Type EXPERIMENTAL

Amiloride

Intervention Type DRUG

Amiloride Nasal Spray

0.4 mg

Group Type EXPERIMENTAL

Amiloride

Intervention Type DRUG

Amiloride Nasal Spray

0.6 mg

Group Type EXPERIMENTAL

Amiloride

Intervention Type DRUG

Amiloride Nasal Spray

Interventions

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Amiloride

Amiloride Nasal Spray

Intervention Type DRUG

Amiloride

Amiloride Nasal Spray

Intervention Type DRUG

Amiloride

Amiloride Nasal Spray

Intervention Type DRUG

Other Intervention Names

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Midamor Midamor Midamor

Eligibility Criteria

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Inclusion Criteria

* Males between 18 to 30 years of age.
* Females between 18 to 30 years of age.
* Provide written informed consent and authorization.
* Study participants must be able to complete consent, all study evaluations, olfactory testing, and study-related health questionnaires written in the English language.

Exclusion Criteria

* History of chronic drug, or narcotic abuse.
* Chronic use of tranquilizers, sedatives, aspirin, antibiotics, or other medications.
* Non-English speaking / English translation services required
* Unwilling or unable to provide informed, written consent.
* History or presence of major organ dysfunction.
* History of malignancy, stroke, or diabetes; cardiac, renal, liver, or severe gastrointestinal disease; or other serious illness.
* History of conditions which might contraindicate or require caution be used in the administration of amiloride including hyperkalemia with elevated serum potassium levels (greater than 5.5 mEq per liter), currently receiving other potassium-conserving agents such as spironolactone or triamterene, currently receiving potassium supplementation in the form of medication, potassium-containing salt substitutes or a potassium-rich diet, history or diagnosis of hypersensitivity to Amiloride.
* Subjects with abnormal kidney function tests \[estimated glomerular filtration (eGFR) - \< 60, and albumin to creatinine ratio (ACR) - \> 30\]
* Female subjects who are pregnant or nursing at the time of screening.
* Subjects who underwent any kind of surgery of nose and septum within the past one year.
* Subjects diagnosed with chronic rhinosinusitis.
* Treatment with any other investigational drug during the 30 days prior to enrollment into the study.
* Subjects who smoke, have a history of smoking or use nicotine-containing products.
* Subjects who have donated blood within 30 days prior to study entry, including that withdrawn during the conduct of any other clinical study.
* Subjects presenting with acute illness.
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Center for Addiction and Mental Health

UNKNOWN

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role lead

Responsible Party

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Venkata Yellepeddi

Associate Professor, Division of Clinical Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Venkata K Yellepeddi, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

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University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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Weissman MM, Klerman GL, Markowitz JS, Ouellette R. Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med. 1989 Nov 2;321(18):1209-14. doi: 10.1056/NEJM198911023211801.

Reference Type BACKGROUND
PMID: 2797086 (View on PubMed)

Grant BF, Saha TD, Ruan WJ, Goldstein RB, Chou SP, Jung J, Zhang H, Smith SM, Pickering RP, Huang B, Hasin DS. Epidemiology of DSM-5 Drug Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III. JAMA Psychiatry. 2016 Jan;73(1):39-47. doi: 10.1001/jamapsychiatry.2015.2132.

Reference Type BACKGROUND
PMID: 26580136 (View on PubMed)

Meuret AE, Rosenfield D, Wilhelm FH, Zhou E, Conrad A, Ritz T, Roth WT. Do unexpected panic attacks occur spontaneously? Biol Psychiatry. 2011 Nov 15;70(10):985-91. doi: 10.1016/j.biopsych.2011.05.027. Epub 2011 Jul 23.

Reference Type BACKGROUND
PMID: 21783179 (View on PubMed)

Maddock RJ, Buonocore MH, Miller AR, Yoon JH, Soosman SK, Unruh AM. Abnormal activity-dependent brain lactate and glutamate+glutamine responses in panic disorder. Biol Psychiatry. 2013 Jun 1;73(11):1111-9. doi: 10.1016/j.biopsych.2012.12.015. Epub 2013 Jan 17.

Reference Type BACKGROUND
PMID: 23332354 (View on PubMed)

Battaglia M, Pesenti-Gritti P, Medland SE, Ogliari A, Tambs K, Spatola CA. A genetically informed study of the association between childhood separation anxiety, sensitivity to CO(2), panic disorder, and the effect of childhood parental loss. Arch Gen Psychiatry. 2009 Jan;66(1):64-71. doi: 10.1001/archgenpsychiatry.2008.513.

Reference Type BACKGROUND
PMID: 19124689 (View on PubMed)

Spatola CA, Scaini S, Pesenti-Gritti P, Medland SE, Moruzzi S, Ogliari A, Tambs K, Battaglia M. Gene-environment interactions in panic disorder and CO(2) sensitivity: Effects of events occurring early in life. Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):79-88. doi: 10.1002/ajmg.b.31144. Epub 2010 Nov 30.

Reference Type BACKGROUND
PMID: 21184587 (View on PubMed)

D'Amato FR, Zanettini C, Lampis V, Coccurello R, Pascucci T, Ventura R, Puglisi-Allegra S, Spatola CA, Pesenti-Gritti P, Oddi D, Moles A, Battaglia M. Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay. PLoS One. 2011 Apr 8;6(4):e18637. doi: 10.1371/journal.pone.0018637.

Reference Type BACKGROUND
PMID: 21494633 (View on PubMed)

Cittaro D, Lampis V, Luchetti A, Coccurello R, Guffanti A, Felsani A, Moles A, Stupka E, D' Amato FR, Battaglia M. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes. Sci Rep. 2016 Apr 28;6:25131. doi: 10.1038/srep25131.

Reference Type BACKGROUND
PMID: 27121911 (View on PubMed)

Giannese F, Luchetti A, Barbiera G, Lampis V, Zanettini C, Knudsen GP, Scaini S, Lazarevic D, Cittaro D, D'Amato FR, Battaglia M. Conserved DNA Methylation Signatures in Early Maternal Separation and in Twins Discordant for CO2 Sensitivity. Sci Rep. 2018 Feb 2;8(1):2258. doi: 10.1038/s41598-018-20457-3.

Reference Type BACKGROUND
PMID: 29396481 (View on PubMed)

Smoller JW, Gallagher PJ, Duncan LE, McGrath LM, Haddad SA, Holmes AJ, Wolf AB, Hilker S, Block SR, Weill S, Young S, Choi EY, Rosenbaum JF, Biederman J, Faraone SV, Roffman JL, Manfro GG, Blaya C, Hirshfeld-Becker DR, Stein MB, Van Ameringen M, Tolin DF, Otto MW, Pollack MH, Simon NM, Buckner RL, Ongur D, Cohen BM. The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function. Biol Psychiatry. 2014 Dec 1;76(11):902-10. doi: 10.1016/j.biopsych.2013.12.018. Epub 2014 Jan 18.

Reference Type BACKGROUND
PMID: 24529281 (View on PubMed)

Battaglia M, Rossignol O, Bachand K, D'Amato FR, De Koninck Y. Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment. J Psychopharmacol. 2019 Jan;33(1):101-108. doi: 10.1177/0269881118784872. Epub 2018 Jul 3.

Reference Type BACKGROUND
PMID: 29968500 (View on PubMed)

Chapman CD, Frey WH 2nd, Craft S, Danielyan L, Hallschmid M, Schioth HB, Benedict C. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013 Oct;30(10):2475-84. doi: 10.1007/s11095-012-0915-1. Epub 2012 Nov 8.

Reference Type BACKGROUND
PMID: 23135822 (View on PubMed)

Yellepeddi VK. Stability of extemporaneously prepared preservative-free prochlorperazine nasal spray. Am J Health Syst Pharm. 2018 Jan 1;75(1):e28-e35. doi: 10.2146/ajhp160531.

Reference Type BACKGROUND
PMID: 29273610 (View on PubMed)

Knowles MR, Church NL, Waltner WE, Yankaskas JR, Gilligan P, King M, Edwards LJ, Helms RW, Boucher RC. Aerosolized amiloride as treatment of cystic fibrosis lung disease: a pilot study. Adv Exp Med Biol. 1991;290:119-28; discussion 129-32. doi: 10.1007/978-1-4684-5934-0_14. No abstract available.

Reference Type BACKGROUND
PMID: 1950741 (View on PubMed)

Knowles MR, Church NL, Waltner WE, Yankaskas JR, Gilligan P, King M, Edwards LJ, Helms RW, Boucher RC. A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis. N Engl J Med. 1990 Apr 26;322(17):1189-94. doi: 10.1056/NEJM199004263221704.

Reference Type BACKGROUND
PMID: 2157983 (View on PubMed)

Noone PG, Regnis JA, Liu X, Brouwer KL, Robinson M, Edwards L, Knowles MR. Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways. Chest. 1997 Nov 5;112(5):1283-90. doi: 10.1378/chest.112.5.1283.

Reference Type BACKGROUND
PMID: 9367469 (View on PubMed)

Olivier KN, Bennett WD, Hohneker KW, Zeman KL, Edwards LJ, Boucher RC, Knowles MR. Acute safety and effects on mucociliary clearance of aerosolized uridine 5'-triphosphate +/- amiloride in normal human adults. Am J Respir Crit Care Med. 1996 Jul;154(1):217-23. doi: 10.1164/ajrccm.154.1.8680683.

Reference Type BACKGROUND
PMID: 8680683 (View on PubMed)

Sood N, Bennett WD, Zeman K, Brown J, Foy C, Boucher RC, Knowles MR. Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects. Am J Respir Crit Care Med. 2003 Jan 15;167(2):158-63. doi: 10.1164/rccm.200204-293OC. Epub 2002 Oct 31.

Reference Type BACKGROUND
PMID: 12411282 (View on PubMed)

Related Links

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https://www.janssen.com/janssen-announces-us-fda-approval-spravato-esketamine-ciii-nasal-spray-adults-treatment-resistant

FDA Approval of SPRAVATO™ (esketamine) CIII Nasal Spray for Adults with Treatment-Resistant Depression

Other Identifiers

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126328

Identifier Type: -

Identifier Source: org_study_id

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