Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000560998
Ethics application status
Approved
Date submitted
16/04/2020
Date registered
13/05/2020
Date last updated
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled, 60-Week, Phase II Clinical Trial of Three Re-Purposed Medications in Moderate Severity Parkinson’s Disease
Scientific title
A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled, 60-Week, Phase II Clinical Trial on the effect of Three Re-Purposed Medications on Moderate Severity Parkinson’s Disease
Secondary ID [1] 296027 0
APM001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson’s Disease 316375 0
Condition category
Condition code
Neurological 314633 314633 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase II study aims to establish the efficacy of three IPs individually in slowing the progression of motor symptoms of moderate severity PD and in maintaining this effect for 12 weeks after the IP is discontinued.

Patients will be randomised to one of the three IPs or placebo in this parallel-group design study. The IPs will be over-encapsulated for blinding purposes and will be administered
along with matching placebos.
Each patient will receive two oral doses, one in the morning and one in the evening, according to the following schedule:
• once a day IPs will be administered with a matching placebo as the second “dose”. Once a day IP will be taken in the morning with matching placebo in the evening
• Twice a day IP will be taken in the morning and evening (no placebo)
• In the placebo arm, placebo will be administered in the morning and evening
The treatments administered are:
1. Alogliptin Arm: Alogliptin tablets, 25 mg once a day + Placebo
2. Albuterol Arm: Albuterol sustained-release (SR) tablets, 8 mg twice a day
3. Nilvadipine Arm: Nilvadipine tablets, 4 mg twice a day
4. Placebo Arm: Placebo administered twice a day

Duration of Treatment: 48 weeks of treatment[additional up to 2 weeks of screening;
follow-up visit 12 weeks after end of treatment]
Route of Administration: All IPs will be taken orally
Strategies used to monitor adherence to the intervention: IP returns, laboratory tests, patient safety checks, patient diaries and questionnaires.
Intervention code [1] 316925 0
Treatment: Drugs
Comparator / control treatment
Matching Placebo- Microcrystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 322962 0
To test three IPs for their ability to slow the progression of motor symptoms in Parkinson's disease patients.
This will be evaluated in the “OFF” usual PD medication state at the end of the 60-week study period.

Outcome is assessed based on MDS-UPDRS (Movement Disorder Society Unified Parkinson’s Disease Rating Scale).
Timepoint [1] 322962 0
Throughout the study (baseline and week 48 and 60, 12 weeks after end of treatment)
Secondary outcome [1] 380384 0
To assess for cognitive performance [Montreal Cognitive Assessment (MoCA)] for each of the IPs during and after the IP treatment period
Timepoint [1] 380384 0
Measured at 48 and 60 weeks compared to baseline.
Secondary outcome [2] 380385 0
To determine the patient’s overall global impression of status at each visit.
Measured by using PGIC(Patient’s Global Impression of Change) for each of the IPs.
Timepoint [2] 380385 0
Visit 12, 24, 48, and 60 weeks compared to baseline.

Eligibility
Key inclusion criteria
Inclusion Criteria
1. Ability to provide written informed consent in accordance with GCP, ICH, and local regulations
2. Male or female aged 25 to 80 (inclusive) as of the date of baseline visit
3. Diagnosis of idiopathic PD according to QSBB criteria
4. PD Modified Hoehn and Yahr stage equal to 2.5 in the “ON” usual PD medication state
5. Must be stabilised on optimal dopaminergic PD treatment for a minimum of
4 weeks prior to the screening visit with no changes in dosing or PD medication expected throughout the study
6. (LFTs: ALT and AST less than or equal to 3 × ULN; total bilirubin less than or equal to 1.5 × ULN; serum albumin greater than or equal to 2.8 g/dL
7. (WOCBP must have a negative serum pregnancy test hCG at screening. WOCBP and men must agree to use highly effective, double barrier contraception during the study. Double barrier contraception is defined as a condom and one other form of the following:
a. Contraceptive pill
b. Depot or injectable birth control
c. Intrauterine Device
d. Contraceptive skin implant, e.g. Implanon NXT®
e. Hormonal vaginal ring, e.g., NuvaRing®
f. Documented evidence of surgical sterilization at least 6 months prior to the screening visit, i.e., tubal ligation or hysterectomy for women or vasectomy for men. Must be willing to remain on their current form of contraception for the duration of the study.
8. Willing and able to have the types of diagnostic procedures required by the protocol, such as phlebotomy and other testing
9. Willing and able to take oral drug therapy according to the study protocol
Minimum age
25 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
1. Confirmed or suspected atypical or parkinsonian syndromes due to drugs, metabolic disorders, encephalitis, cerebrovascular disease or neurodegenerative diseases
2. Females who are pregnant or breastfeeding
3. Body mass index less than 18.5
4. Prior surgical intervention for PD (including but not limited to DBS, tDCS,
NIr therapy or cell transplantation) or active continuous infusion therapy
(including but not limited to Duodopa® and/or apomorphine)
5. Any known hypersensitivity to any of the three IPs or their constituents
6. Received any of the following drugs within 30 days prior to the first dose of study product or 5 half-lives, whichever is longer:
a. Any of the three IPs
b. Any asthma medication/s which have ß2 adrenergic agonist action (e.g., budesonide with formoterol)
c. CCB medication
d. ß-blocker medication
e. Prochlorperazine
f. Metoclopramide hydrochloride
g. CoQ10
h. Oral or sublingual supplements which may contain nicotinamide,
including but not limited to:
i. nicotinamide tablets
ii. niacinamide tablets
iii. vitamin B3 tablets
iv. vitamin B complex
v. any NAD+ potential booster
vi. any other over the counter medication which may interfere with the outcomes of the study
7. Exposed to typical or atypical antipsychotics or other dopamine blocking agents
within 6 months prior to screening
8. Gastrointestinal conditions that may affect the absorption of IP (e.g. ulcerative colitis, gastric bypass)
9. Diagnosis of T1DM or T2DM, for which drug treatment is prescribed 10. History of significant medical event/s within 6 months prior to the screening visit, at the discretion of the PI. This includes, but is not limited to a cerebrovascular event or a myocardial infarction
11. Serious neurological disorder other than PD
12. History of head trauma with loss of consciousness for more than 5 minutes within the past 6 months
13. Sustained supine hypertension equal to 180 mmHg systolic or 110 mmHg diastolic;
sustained is defined as the average of three observations, each at least 10 minutes apart, with the patient having been supine and at rest for at least 5 minutes prior to each measurement
14. History of symptomatic OH which interferes with the patient’s day-to-day level of functioning. OH is defined as a decrease of greater than or equal to 20 mmHg systolic or
greater than or equal to 10 mmHg diastolic when changing from supine to standing position, after having been in supine position for at least 5 minutes
15. Any significant uncontrolled cardiac arrhythmia, including but not limited to second and third degree AV block
16. Current unstable angina
17. Congestive heart failure (NYHA Class 3 or 4)
18. Heart rate lesser than or equal to 50 bpm as tested on three occasions 10 minutes apart
19. Abnormal 12-lead ECG results which, in the opinion of the Investigator, will prevent participation in the study
20. Prior diagnosis of cancer and evidence of continued malignancy within the past 3 years (with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or in situ prostate cancer with normal prostate-specific antigens post resection)
21. Any major surgical procedure within 30 days prior to the screening visit
22. Severely impaired renal function with creatinine clearance less than 30 mL/min
23. Diagnosis of dementia as defined by MDS PD Dementia criteria
24. Active alcohol or substance use disorder within the past 12 months
25. Depression of moderate severity or more on the Patient Health Questionnaire (PHQ-9) greater than or equal to 10 at the screening visit
26. History of psychotic symptoms requiring antipsychotic treatment, or history of a suicidal attempt/s within the prior 6 months
27. Any condition or laboratory test result, which in the Investigator's judgment might result in an increased risk to the patient or would affect their participation in the study
28. Participation in any trial of a device (including, but not limited to TMS), drug supplement, NIr and red light therapy, investigational medicinal product, supplement, surgical treatment, cognitive/behavioural therapy, physiotherapy or active exercise study within 30 days prior to the screening visit.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2020
Actual
Date of last participant enrolment
Anticipated
1/04/2021
Actual
Date of last data collection
Anticipated
1/07/2022
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA,VIC
Recruitment hospital [1] 15963 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 15970 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 15973 0
Hollywood Private Hospital - Nedlands
Recruitment hospital [4] 15975 0
The Alfred - Melbourne
Recruitment hospital [5] 15976 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [6] 15977 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 29456 0
5000 - Adelaide
Recruitment postcode(s) [2] 29461 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 29464 0
6009 - Nedlands
Recruitment postcode(s) [4] 29466 0
3004 - Melbourne
Recruitment postcode(s) [5] 29467 0
2109 - Macquarie Park
Recruitment postcode(s) [6] 29468 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 300617 0
University
Name [1] 300617 0
University of Sydney
Country [1] 300617 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Brain and Mind Centre, 100 Mallett St, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 300122 0
None
Name [1] 300122 0
Address [1] 300122 0
Country [1] 300122 0
Other collaborator category [1] 281212 0
Commercial sector/Industry
Name [1] 281212 0
Novotech (Australia) Pty Limited
Address [1] 281212 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 281212 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301405 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 301405 0
L8 Harold Stokes Building,
145 Studley Road, Heidelberg
PO Box 5555, Victoria, 3084
Ethics committee country [1] 301405 0
Australia
Date submitted for ethics approval [1] 301405 0
17/02/2020
Approval date [1] 301405 0
23/03/2020
Ethics approval number [1] 301405 0
Ethics committee name [2] 305447 0
Bellberry Ltd Human Research Ethics Committee
Ethics committee address [2] 305447 0
Bellberry Limited
123 Glen Osmond Road,
Eastwood SA 5063
Ethics committee country [2] 305447 0
Australia
Date submitted for ethics approval [2] 305447 0
Approval date [2] 305447 0
11/03/2020
Ethics approval number [2] 305447 0
Ethics committee name [3] 305462 0
Macquarie University Human Research Ethics Committee
Ethics committee address [3] 305462 0
Alumni Relations
Building 1
58 Waterloo Road
Macquarie University
NSW 2113 Australia
Ethics committee country [3] 305462 0
Australia
Date submitted for ethics approval [3] 305462 0
Approval date [3] 305462 0
Ethics approval number [3] 305462 0

Summary
Brief summary
This Phase II study aims to establish the efficacy of three IPs individually in slowing the progression of motor symptoms of moderate severity PD and in maintaining this effect for 12 weeks after the IP is discontinued. This is to rule out an unexpected symptomatic rather than disease-modifying benefit. Patients with moderate severity PD, on a stable dose of usual PD medication [L-dopa, dopamine agonists, COMT inhibitors, MAO inhibitors and/or amantadine], will be randomised to one of the three IPs or placebo in this parallel-group design study. The IPs will be over-encapsulated for blinding purposes and will be administered along with matching placebos. All patients will receive two oral capsules per day, according to the following schedule:
• Twice daily (BID) IP will be taken in the morning and evening (no placebo)
• Once daily (QD) IP will be taken in the morning with matching placebo in the evening (as a second “dose”)
• Placebo will be taken in the morning and evening
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86890 0
Dr Simon JG Lewis
Address 86890 0
University of Sydney, Brain and Mind Centre, 100 Mallett St, Camperdown NSW 2050
Country 86890 0
Australia
Phone 86890 0
+61 02 9114 4121
Fax 86890 0
Email 86890 0
profsimonlewis@gmail.com
Contact person for public queries
Name 86891 0
Ms Jennifer Maschmann
Address 86891 0
Novotech (Australia) Pty Limited, Level 2, 15-31 Pelham Street Carlton VIC 3053 Australia
Country 86891 0
Australia
Phone 86891 0
+61 03 9341 1963
Fax 86891 0
Email 86891 0
Jennifer.Maschmann@novotech-cro.com
Contact person for scientific queries
Name 86892 0
Dr Carolynne Darby
Address 86892 0
Novotech (Australia) Pty Limited, Level 3, 235 Pyrmont Street Pyrmont, NSW, 2009 Australia
Country 86892 0
Australia
Phone 86892 0
+61 0 432 397 254
Fax 86892 0
Email 86892 0
Carolynne.Darby@novotech-cro.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not Applicable


What supporting documents are/will be available?

No Supporting Document Provided
Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.