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Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease

Information source: Northwestern University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Parkinson Disease

Intervention: Isradipine CR 5mg (Drug); Isradipine CR 10mg (Drug); Isradipine CR 20mg (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Northwestern University

Official(s) and/or principal investigator(s):
Tanya Simuni, MS, Study Chair, Affiliation: Northwestern University


The primary purpose of this study is to establish a dosage of isradipine CR that is tolerable and demonstrates preliminary efficacy for utilization in future pivotal efficacy studies.

Clinical Details

Official title: A Pilot Phase II Double-Blind, Placebo-Controlled, Tolerability and Dosage Finding Study of Isradipine CR as a Disease Modifying Agent in Patients With Early Parkinson Disease

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR.

Secondary outcome:

Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS)

Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale

Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale

Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale

Efficacy: Change in Modified Hoehn & Yahr Scale

Efficacy: Change in Modified Schwab & England Independence Scale

Efficacy: Change in Beck Depression Inventory II (BDI-II)

Efficacy: Change in Montreal Cognitive Assessment

Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39)

Vital Signs: Change in Systolic Standing

Vital Signs: Change in Systolic Supine

Vital Signs: Change in Diastolic Standing

Vital Signs: Change in Diastolic Supine

Vital Signs: Change in Pulse Standing

Vital Signs: Change in Pulse Supine

Common Adverse Events: Oedema Peripheral

Common Adverse Events: Dizziness

Common Adverse Events: Nasopharyngitis

Common Adverse Events: Headache

Common Adverse Events: Constipation

Common Adverse Events: Fatigue

Common Adverse Events: Nausea

Common Adverse Events: Upper Respiratory Tract Infection

Common Adverse Events: Depression

Common Adverse Events: Somnolence

Common Adverse Events: Insomnia

Common Adverse Events: Dyspepsia

Common Adverse Events: Diarrhoea

Common Adverse Events: Sinusitis

Common Adverse Events: Back Pain

Common Adverse Events: Hypotension

Detailed description: There is solid scientific rational and preclinical data supporting a clinical trial of isradipine CR as a potential disease modifying agent in early PD. Human pharmacokinetic data demonstrate that it is feasible to achieve the serum concentrations in humans that were neuroprotective in preclinical models with the FDA approved dosage range. Pilot data demonstrate acceptable tolerability of isradipine CR in the PD population. Tolerability is inversely proportional to the dosage dependent. Considering that tolerability of isradipine CR is inversely proportional to the dosage exposure, it is essential to proceed with the dose selection tolerability study in preparation for the future efficacy trials. The tolerability, defined as the ability to complete the study, of three dosages of isradipine CR relative to placebo in subjects with early Parkinson's disease will be examined first. The dosage that is tolerable and demonstrates preliminary efficacy will be evaluated further in the future pivotal efficacy studies.


Minimum age: 30 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria:

- Subjects with early idiopathic PD. If tremor is not present, subjects must have

unilateral onset and persistent asymmetry of the symptoms.

- Be over 30 years old at the time of diagnosis of PD.

- Hoehn & Yahr stage is less than or equal to 2. 5.

- Currently not receiving dopaminergic therapy and not projected to require

dopaminergic therapy for at least 6 months from enrollment.

- Use of MAO-B inhibitors (rasagiline, selegiline), amantadine, or anticholinergics

will be allowed. The dosage has to be stable for 3 months prior to baseline visit and throughout the duration of the study. Exclusion Criteria:

- Subjects with a diagnosis of an atypical Parkinsonism

- Subjects unwilling or unable to give informed consent

- Use of CoQ10 at a dosage >600mg daily or use of creatine >5 grams daily within the 60

days prior to randomization

- Exposure to dopaminergic PD therapy within 60 days prior to enrollment or for 3

months or more at any point in the past

- History of clinically significant orthostatic hypotension or presence of orthostatic

hypotension at the screening visit defined as > 20 mmHg change in systolic BP and >10mm change in diastolic BP after 2 min of standing, or baseline BP <90/60

- History of congestive heart failure

- History of bradycardia defined as heart rate <55

- Presence of 2nd or 3rd degree atrioventricular block or other significant ECG

abnormalities that in the investigator's opinion would compromise participation in study

- Clinically significant abnormalities in the Screening Visit laboratory studies or


- Presence of other known medical or psychiatric comorbidity that in the investigator's

opinion would compromise participation in the study

- Prior exposure to isradipine or other calcium channel blockers within 6 months of


- Subjects with history of hypertension treated with a maximum of 2 other

antihypertensive agents will be allowed provided that the doses of concomitant anti HTN therapy can be reduced/adjusted during the study based on the BP readings in consultation with the subject's primary care physician or cardiologist.

- Use of grapefruit juice, Ginkgo biloba, St. John's wart and/or ginseng will be

prohibited during the study (as they interfere with the metabolism of isradipine).

- Presence of cognitive dysfunction defined by a Mini Mental Status Exam ( MMSE) score

< 26 at screening

- Subjects with clinically significant depression as determined by a Beck Depression

Inventory (BDI) score >15 at screening

- History of exposure to typical or atypical antipsychotics or other dopamine blocking

agents within 6 months prior to enrollment

- Subjects have to be on a stable regimen of central nervous system acting medications

(benzodiazepines, antidepressants, hypnotics) for 30 days prior to enrollment

- Lactating women or women of childbearing potential who are not surgically sterilized

have to use a reliable measure of contraception and have a negative serum pregnancy test at screening

- Participation in other investigational drug trials within 30 days prior to screening

- History of brain surgery for PD

Locations and Contacts

Parkinson Institute, Sunnyvale, California 94805, United States

Institute for Neurodegenerative Disorders, New Haven, Connecticut 06510, United States

Mayo Clinic Jacksonville, Jacksonville, Florida 32224, United States

University of Miami, Miami, Florida 33136, United States

University of South Flordia, Tampa, Florida 33606, United States

Emory University School of Medicine, Atlanta, Georgia 30329, United States

Pacific Health Institute, Honolulu, Hawaii 96817, United States

Northwestern University, Chicago, Illinois 60611, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Boston University, Boston, Massachusetts 02118, United States

Michigan State University, East Lansing, Michigan 48824, United States

Park Nicolet Clinic, Golden Valley, Minnesota 55427, United States

University of Minnesota, Minneapolis, Minnesota 55455, United States

Washington University, St. Louis, Missouri 63110, United States

University of Rochester, Rochester, New York 14618, United States

University of Cincinnati, Cincinnati, Ohio 45219, United States

Ottowa Hospital Civic Site, Ottawa, Ontario K1Y 4E9, Canada

Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada

University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

University of Tennessee, Memphis, Tennessee 38104, United States

Additional Information

Related publications:

Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328(3):176-83.

Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002 Apr 3;287(13):1653-61.

Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol. 2004 Apr;61(4):561-6.

NINDS NET-PD Investigators. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006 Mar 14;66(5):664-71. Epub 2006 Feb 15.

NINDS NET-PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007 Jan 2;68(1):20-8.

Becker C, Jick SS, Meier CR. Use of antihypertensives and the risk of Parkinson disease. Neurology. 2008 Apr 15;70(16 Pt 2):1438-44. doi: 10.1212/01.wnl.0000303818.38960.44. Epub 2008 Feb 6.

Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004 Oct;318(1):121-34. Epub 2004 Aug 24. Review.

Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature. 2007 Jun 28;447(7148):1081-6. Epub 2007 Jun 10.

Christensen HR, Antonsen K, Simonsen K, Lindekaer A, Bonde J, Angelo HR, Kampmann JP. Bioavailability and pharmacokinetics of isradipine after oral and intravenous administration: half-life shorter than expected? Pharmacol Toxicol. 2000 Apr;86(4):178-82.

de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 Jun;5(6):525-35. Review.

Dodel RC, Singer M, Köhne-Volland R, Szucs T, Rathay B, Scholz E, Oertel WH. The economic impact of Parkinson's disease. An estimation based on a 3-month prospective analysis. Pharmacoeconomics. 1998 Sep;14(3):299-312.

Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007 Jan 30;68(5):384-6. Epub 2006 Nov 2.

Elm JJ, Goetz CG, Ravina B, Shannon K, Wooten GF, Tanner CM, Palesch YY, Huang P, Guimaraes P, Kamp C, Tilley BC, Kieburtz K; NET-PD Investigators. A responsive outcome for Parkinson's disease neuroprotection futility studies. Ann Neurol. 2005 Feb;57(2):197-203.

Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K; Parkinson Study Group. Levodopa and the progression of Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2498-508.

Gill DJ, Freshman A, Blender JA, Ravina B. The Montreal cognitive assessment as a screening tool for cognitive impairment in Parkinson's disease. Mov Disord. 2008 May 15;23(7):1043-6. doi: 10.1002/mds.22017.

Goetz CG, LeWitt PA, Weidenman M. Standardized training tools for the UPDRS activities of daily living scale: newly available teaching program. Mov Disord. 2003 Dec;18(12):1455-8.

Goetz CG, Stebbins GT, Chmura TA, Fahn S, Klawans HL, Marsden CD. Teaching tape for the motor section of the unified Parkinson's disease rating scale. Mov Disord. 1995 May;10(3):263-6.

Huse DM, Schulman K, Orsini L, Castelli-Haley J, Kennedy S, Lenhart G. Burden of illness in Parkinson's disease. Mov Disord. 2005 Nov;20(11):1449-54.

Jankovic J, Hunter C. A double-blind, placebo-controlled and longitudinal study of riluzole in early Parkinson's disease. Parkinsonism Relat Disord. 2002 Mar;8(4):271-6.

Johnson BA, Javors MA, Lam YW, Wells LT, Tiouririne M, Roache JD, Ait-Daoud N, Lawson K. Kinetic and cardiovascular comparison of immediate-release isradipine and sustained-release isradipine among non-treatment-seeking, cocaine-dependent individuals. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):15-20. Epub 2004 Nov 11.

Kupsch A, Sautter J, Schwarz J, Riederer P, Gerlach M, Oertel WH. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in non-human primates is antagonized by pretreatment with nimodipine at the nigral, but not at the striatal level. Brain Res. 1996 Nov 25;741(1-2):185-96.

Leentjens AF, Verhey FR, Luijckx GJ, Troost J. The validity of the Beck Depression Inventory as a screening and diagnostic instrument for depression in patients with Parkinson's disease. Mov Disord. 2000 Nov;15(6):1221-4.

Levy G, Kaufmann P, Buchsbaum R, Montes J, Barsdorf A, Arbing R, Battista V, Zhou X, Mitsumoto H, Levin B, Thompson JL. A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS. Neurology. 2006 Mar 14;66(5):660-3.

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9.

Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology. 2001 Jun;56(11 Suppl 5):S1-S88. Review.

Peto V, Jenkinson C, Fitzpatrick R, Greenhall R. The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease. Qual Life Res. 1995 Jun;4(3):241-8.

Richards M, Marder K, Cote L, Mayeux R. Interrater reliability of the Unified Parkinson's Disease Rating Scale motor examination. Mov Disord. 1994 Jan;9(1):89-91.

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50.

Simuni T, Borushko E, Avram MJ, Miskevics S, Martel A, Zadikoff C, Videnovic A, Weaver FM, Williams K, Surmeier DJ. Tolerability of isradipine in early Parkinson's disease: a pilot dose escalation study. Mov Disord. 2010 Dec 15;25(16):2863-6. doi: 10.1002/mds.23308.

Striessnig J, Koschak A, Sinnegger-Brauns MJ, Hetzenauer A, Nguyen NK, Busquet P, Pelster G, Singewald N. Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem Soc Trans. 2006 Nov;34(Pt 5):903-9.

Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):976-82. Erratum in: Neurology. 2006 Jul 25;67(2):299.

Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies of Parkinson's disease. Mov Disord. 2003 Jan;18(1):19-31. Review.

Urien S, Pinquier JL, Paquette B, Chaumet-Riffaud P, Kiechel JR, Tillement JP. Effect of the binding of isradipine and darodipine to different plasma proteins on their transfer through the rat blood-brain barrier. Drug binding to lipoproteins does not limit the transfer of drug. J Pharmacol Exp Ther. 1987 Jul;242(1):349-53.

Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ; REAL-PET Study Group. Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol. 2003 Jul;54(1):93-101.

Zadikoff C, Fox SH, Tang-Wai DF, Thomsen T, de Bie RM, Wadia P, Miyasaki J, Duff-Canning S, Lang AE, Marras C. A comparison of the mini mental state exam to the Montreal cognitive assessment in identifying cognitive deficits in Parkinson's disease. Mov Disord. 2008 Jan 30;23(2):297-9.

Starting date: July 2009
Last updated: April 16, 2013

Page last updated: August 20, 2015

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