None listed
Conditions
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
Interventions
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
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.
Sponsors
University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
25 Years to 80 Years
Healthy volunteers
No
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
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 deep brain stimulation (DBS), Transcranial Direct-Current Stimulation (tDCS), Near infrared light (NIr) therapy or cell transplantation] or active continuous infusion therapy (including but not limited to Duodopa® and/or apomorphine). Patients who have used the following therapies may be considered if the relevant washout period is completed: a. Over the counter therapies (eg, vitamin supplements) would require a washout period of 1 month (30 days) from screening. The use of PD-modifying over the counter vitamin supplements (eg, co-enzyme Q10, vitamin E and nicotinamide) is prohibited during the study. b. Other therapies where there might be a symptomatic effect (eg, red light therapy, tDCS) would require a washout period of a minimum of 12 weeks from screening. c. Previous disease-modifying or systematic IPs would require a washout period of at least five times the half-life of the treatment. 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 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 sitting 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 sitting 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 or sitting to standing position, after having been in supine or sitting 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. Patients with heart rate < 50 bpm due to sinus bradycardia may be included at the discretion of the Investigator following discussion with the Sponsor and Medical Monitor. 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. Patients with scores above = 10, with no clinical signs of depression, can be included at the discretion of the Investigator following discussion with the Sponsor and Medical Monitor. 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.. Patients who have used the following therapies may be considered if the relevant washout period is completed: a. Over the counter therapies (eg, vitamin supplements) would require a washout period of 1 month (30 days) from screening. The use of PD-modifying over the counter vitamin supplements (eg, co-enzyme Q10, vitamin E and nicotinamide) is prohibited during the study. b. Other therapies where there might be a symptomatic effect (eg, red light therapy, tDCS) would require a washout period of a minimum of 12 weeks from screening. c. Previous disease-modifying or systematic IPs would require a washout period of at least five times the half-life of the treatment.
Outcome results
None listed