Alzheimer DiseasePhase 3DOPAD-3NCT06702124
A Phase 3 Study of Rotigotine in Combination with Rivastigmine in Mild to Moderate Alzheimer's Disease
A Phase 3 study testing Rotigotine 4Mg/24Hrs Patch in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 1 site in Italy.
Trial summary
This is a 24-week prospective, randomized, double-blind, placebo-controlled, multi-center phase III study evaluating efficacy and safety of rotigotine 4mg/24 hrs in combination with rivastigmine 9.5 mg/24 hrs in mild to moderate AD patients. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Rotigotine 4Mg/24Hrs Patch
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 348 participants
- Where
- 1 siteItaly
- Study dates
- 1 Dec 2023to Apr 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women (non-childbearing potential, as defined in Appendix 2) with a diagnosis of AD according to IWG criteria
- Age 50-85 years
- MRI or computerized tomography (CT) assessment, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3)
- Patients who show CSF biomarker data supporting the diagnosis of AD (for Czech Republic only: lumbar punctures can be performed for screening purposes), or patients with a positive Amyloid Pet Scan will qualify for the study
- Stable on a treatment with rivastigmine transdermal patch for at least 3 months, of which at least the last month was at 9.5mg/day, or for one month, if the patient had received donepezil before rivastigmine
- Mild to moderate stage of AD according to MMSE ≥18 and ≤26
Show all 17Show fewer
- Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild)
- Evidence of frontal lobe dysfunctions as assessed by FAB ≤14
- Absence of major depressive disease according to GDS of < 5
- Formal education for five or more years
- Previous decline in cognition for more than six months as documented in patient medical records
- A caregiver available and living in the same household or interacting with the patient and available if necessary to assure administration of drug
- Patients living at home or nursing home setting without continuous nursing care
- General health status acceptable for a participation in a 6-month clinical trial
- Stable pharmacological treatment of any other chronic condition for at least one month prior to screening
- No regular intake of prohibited medications
- Signed informed consent by the patient. If there are any doubts that the patient is mentally capable of giving informed consent, the patient will be examined and verified to be mentally capable by an independent physician/ neurologist, prior to the initiation of any study specific procedure. Signed consent of the caregiver
Who cannot join
- Failure to perform screening or baseline examinations
- Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period
- Clinical, laboratory or neuro-imaging findings consistent with:
- other primary degenerative dementia (dementia with Lewy bodies, fronto- temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.);
- other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.);
- orthostatic hypotension and autonomic disorders
Show all 38Show fewer
- cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter);
- other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.);
- seizure disorder;
- other infectious, metabolic, or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.).
- A current DSM-V diagnosis of active major depression, schizophrenia, or bipolar disorder
- Any suicidal ideation or suicidal behavior in the C-SSRS (C-SSRS score > 0)
- Clinically significant, advanced, or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
- history of any kind of psychosis
- chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN);
- respiratory insufficiency;
- renal insufficiency (serum creatinine >2 mg/dl) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula). In case of creatinine clearance ≤30 mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the patient can be included;
- heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening);
- bradycardia (heart beat <50/min.) or tachycardia (heart beat >95/min);
- hypertension (>140/90 mm/Hg) or hypotension (<90/60 mm/Hg) requiring treatment with more than three drugs;
- AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males >450 and females >470 msec);
- uncontrolled diabetes defined by HbA1c >8.5;
- malignancies within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer;
- metastases;
- disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.);
- women who are fertile and of childbearing potential;
- chronic daily drug intake of ≥ 14 days or expected for ≥ 14 days:
- benzodiazepines, neuroleptics or major sedatives,
- antiepileptics,
- centrally active anti-hypertensive drugs (clonidine, l-methyl DOPA, guanidine, guanfacine, etc.),
- opioid containing analgesics,
- nootropic drugs (except Ginkgo Biloba);
- suspected or known drug or alcohol abuse, i.e., more than approximately 60 g alcohol (approximately 1 liter of beer or 500 ml of wine) per day, indicated by elevated mean corpuscular volume (MCV) above normal value at screening; (Please advise all subjects that because of possible additive effects, patients should not be taking alcohol in combination with rotigotine).
- suspected or known allergy to any components of the study treatments;
- hypersensitivity to the active substance rotigotine or to any of the excipients contained in the patches (according to SmPC).
- enrollment in another investigational study or intake of investigational drug within the previous three months or five times the half-life of the IMP/metabolites (whichever is longer)
- any condition, which, in the opinion of the investigator, makes the patient unsuitable for inclusion;
- if the patient is in any way dependent on the sponsor or the principal investigator or if the patient is accommodated in an establishment on judicial or administrative order.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Santa Lucia Foundation
Rome, Italy, 00179
Fulvia DI Iulio, +390651501829, f.diiulio@hsantalucia.it
About this study
Official title: Effects of Dopaminergic Therapy in Patients with Alzheimer's Disease: a 24 Weeks Prospective, Randomized, Double-blind, Placebo-controlled, Parallel Group, International, Multi-center Phase III Study Evaluating Efficacy and Safety of Rotigotine 4 Mg/24 Hrs in Combination with Rivastigmine 9.5 Mg/24 Hrs in Mild to Moderate Alzheimer's Disease Patients.
This is a 24-week prospective, randomized, double-blind, placebo-controlled, multi-center phase III study evaluating efficacy and safety of rotigotine 4mg/24 hrs in combination with rivastigmine 9.5 mg/24 hrs in mild to moderate AD patients. The total study duration per patient from baseline to the end will be 24 weeks. The study has a placebo-controlled design to eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources.
Read the detailed description
Patients will be screened at trial sites for determination of eligibility to enter the study on the basis of diagnostic evaluations, according to current diagnostic criteria for probable AD, and safety assessments (vital sign complete physical and neurological examinations). The efficacy assessments (cognitive/behavioral evaluations) will be performed at Baseline before starting treatment and repeated ontreatment at Weeks 6, 12 and 24. EEG neurophysiological examinations will be performed at Baseline and at Week 24. Plasma biomarkers will be collected at baseline and at Week 24. Visit windows are ±7 days for all the scheduled visits. At each in-clinic visit (or upon early termination), AEs will be recorded, at screening, baseline, weeks 6, 12 and 24 vital signs measured, and physical and neurological examination performed. During intervening times between visits, caregivers will be contacted by telephone at approximately at Weeks 4 and 16 and an unscheduled visit will take place if needed in response to a safety concern.
- Conditions
- Alzheimer Disease
- Being tested
- Rotigotine 4Mg/24Hrs Patch, Placebo
- Keywords
- Dopamine, Rotigotine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rotigotine 4Mg/24Hrs PatchDrug
Rotigotine 4 mg/24Hrs administration for 24 weeks
PlaceboDrug
Placebo administration for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Rotigotine 4 mg | Experimental | Rotigotine 4 mg/24 hours transdermal patch administration Receives: Drug: Rotigotine 4Mg/24Hrs Patch |
| Placebo | Placebo comparator | Placebo transdermal patch administration Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo.
FAB is a brief battery of six neuropsychological tasks designed to assess frontal lobe function
Measured: From enrollment to the end of 24 weeks of treatment
Secondary outcomes (5)
Change from Baseline to Week 24 in the ADCS-ADL to evaluate efficacy of rotigotine in combination with rivastigmine on autonomies of daily living as compared to rivastigmine in combination with placebo
The ADCS-ADL includes 23 items that were derived from a larger set of items describing performance of activities of daily living
Measured: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the MoCA to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo.
The MoCA is a brief, simple, and reliable screening test for AD. The test checks language, memory, visual and spatial thinking, reasoning, and orientation skills.
Measured: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the CDR-SOB, to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo
The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to AD and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care
Measured: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the ADAS-Cog14 to evaluate efficacy of rotigotine in combination with rivastigmine on memory functions as compared to rivastigmine in combination with placebo.
ADAS-cog assesses the level of cognitive dysfunction in AD. The ADAS-Cog14 consists of items from the following areas chosen for their sensitivity to AD: language; memory; praxis executive functions and orientation.
Measured: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the AMI to evaluate efficacy of rotigotine in combination with rivastigmine on levels of apathy and motivation as compared to rivastigmine in combination with placebo.
The Apathy-Motivation Index was developed as a brief self-report index of apathy and motivation.
Measured: From enrollment to the end of 24 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2024
- Study start1 Dec 2023
- Primary completionJul 2025 (estimated)
- Study completionApr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 348 participants (estimated)
Sponsor and investigators
- Lead sponsor
- I.R.C.C.S. Fondazione Santa Lucia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06702124
- Sponsor's protocol ID
- EU CT Number:2023-504602-11-00
- Acronym
- DOPAD-3
- Status last verified
- Nov 2024
- First submitted
- 12 Nov 2024
- Last updated
- 22 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dopaminergic Therapy in Patients with Alzheimer's Disease: a 24 Weeks Prospective, Randomized, Double-blind, Placebo-controlled, Parallel Group, International, Multi-center Phase III Study Evaluating Efficacy and Safety of Rotigotine 4 Mg/24 Hrs in Combination with Rivastigmine 9.5 Mg/24 Hrs in Mild to Moderate Alzheimer's Disease Patients.
- ClinicalTrials.gov ID
- NCT06702124
- Acronym / sponsor ID
- DOPAD-3 / EU CT Number:2023-504602-11-00
- Conditions
- Alzheimer Disease
- Keywords
- Dopamine, Rotigotine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 348 participants (estimated)
- Lead sponsor
- I.R.C.C.S. Fondazione Santa LuciaUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- Jul 2025 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 22 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 24-week prospective, randomized, double-blind, placebo-controlled, multi-center phase III study evaluating efficacy and safety of rotigotine 4mg/24 hrs in combination with rivastigmine 9.5 mg/24 hrs in mild to moderate AD patients. The total study duration per patient from baseline to the end will be 24 weeks. The study has a placebo-controlled design to eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources.
Detailed description
Patients will be screened at trial sites for determination of eligibility to enter the study on the basis of diagnostic evaluations, according to current diagnostic criteria for probable AD, and safety assessments (vital sign complete physical and neurological examinations). The efficacy assessments (cognitive/behavioral evaluations) will be performed at Baseline before starting treatment and repeated ontreatment at Weeks 6, 12 and 24. EEG neurophysiological examinations will be performed at Baseline and at Week 24. Plasma biomarkers will be collected at baseline and at Week 24. Visit windows are ±7 days for all the scheduled visits. At each in-clinic visit (or upon early termination), AEs will be recorded, at screening, baseline, weeks 6, 12 and 24 vital signs measured, and physical and neurological examination performed. During intervening times between visits, caregivers will be contacted by telephone at approximately at Weeks 4 and 16 and an unscheduled visit will take place if needed in response to a safety concern.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rotigotine 4 mg | Experimental | Drug: Rotigotine 4Mg/24Hrs PatchRotigotine 4 mg/24 hours transdermal patch administration |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo transdermal patch administration |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Men and women (non-childbearing potential, as defined in Appendix 2) with a diagnosis of AD according to IWG criteria
- Age 50-85 years
- MRI or computerized tomography (CT) assessment, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3)
- Patients who show CSF biomarker data supporting the diagnosis of AD (for Czech Republic only: lumbar punctures can be performed for screening purposes), or patients with a positive Amyloid Pet Scan will qualify for the study
- Stable on a treatment with rivastigmine transdermal patch for at least 3 months, of which at least the last month was at 9.5mg/day, or for one month, if the patient had received donepezil before rivastigmine
Key exclusion criteria (38 listed)
- Failure to perform screening or baseline examinations
- Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period
- Clinical, laboratory or neuro-imaging findings consistent with:
- A current DSM-V diagnosis of active major depression, schizophrenia, or bipolar disorder
- Any suicidal ideation or suicidal behavior in the C-SSRS (C-SSRS score > 0)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rotigotine 4Mg/24Hrs PatchRotigotine 4 mg/24Hrs administration for 24 weeks | Drug | Rotigotine 4 mg |
| PlaceboPlacebo administration for 24 weeks | Drug | Placebo |
Primary outcome
Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo.
Time frame: From enrollment to the end of 24 weeks of treatment
FAB is a brief battery of six neuropsychological tasks designed to assess frontal lobe function
5 secondary outcomes
Change from Baseline to Week 24 in the ADCS-ADL to evaluate efficacy of rotigotine in combination with rivastigmine on autonomies of daily living as compared to rivastigmine in combination with placebo
Time frame: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the MoCA to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo.
Time frame: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the CDR-SOB, to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo
Time frame: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the ADAS-Cog14 to evaluate efficacy of rotigotine in combination with rivastigmine on memory functions as compared to rivastigmine in combination with placebo.
Time frame: From enrollment to the end of 24 weeks of treatment
Change from Baseline to Week 24 in the AMI to evaluate efficacy of rotigotine in combination with rivastigmine on levels of apathy and motivation as compared to rivastigmine in combination with placebo.
Time frame: From enrollment to the end of 24 weeks of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rotigotine 4Mg/24Hrs Patch in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giacomo Koch, Prof (+390651501181, g.koch@hsantlucia.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo. (time frame: From enrollment to the end of 24 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025; AzTrials last refreshed its copy on 6 Nov 2026.