Alzheimer's DiseasePhase 1NCT01864655
Safety and Tolerability of AZD0530 (Saracatinib) in Alzheimer's Disease
A Phase 1 study testing saracatinib in people with Alzheimer's Disease, run by Stephen M. Strittmatter at 1 site in United States.
Trial summary
Alzheimer's disease is a devastating neurodegenerative disorder, for which there is currently no effective treatment to slow or halt progression. Beta amyloid peptide accumulates in the brains of those with Alzheimer's, and is thought to play a major role in triggering the dementia. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- saracatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to 6 Nov 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. NIA-Alzheimer's Association core clinical criteria for probable AD 2. Age between 50-90 (inclusive). 3. MMSE score between 16 and 26 (inclusive) 4. Clinical Dementia Rating = 0.5, 1.0, or 2 5. Stability of permitted medications for 4 weeks. In particular, subjects may:
- Take stable doses of antidepressants (if they are not currently depressed or do not have a history of major depression within the past 1 year).
- Washout from psychoactive medication for at least 4 weeks prior to screening.
- Cholinesterase inhibitors are allowable if stable for 12 weeks prior to screen. 6. Geriatric Depression Scale less than 6. 7. Study partner is available who has frequent contact with the subject (e.g. an average of 8 hours per week or more), and can accompany the subject to all clinic visits for the duration of the protocol.
- 8. Visual and auditory acuity adequate for neuropsychological testing. 9. Good general health with no diseases expected to interfere with the study. 10. Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
- 11. Modified Hachinski less than or equal to 4. 12. Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
- 13. Must speak English or Spanish fluently.
Who cannot join
- Any significant neurologic disease other than AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
- Subjects that have any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker will be excluded from the study.
- Major depression, bipolar disorder as described in DSM-IV within the past 1 year. Psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol.
- History of schizophrenia (DSM IV criteria).
- History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
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- Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.
- Clinically significant abnormalities in B12 or TFTs that might interfere with the study.
- Residence in skilled nursing facility.
- Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.
- Investigational amyloid lowering therapies are prohibited two months prior to screening and for the duration of the trial. Other investigational agents are prohibited one month prior to screening and for the duration of the trial.
- Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.
- 7. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results, or the patient's ability to participate in the study.
- 8. Clinically significant abnormalities in B12 or TFTs that might interfere with the study.
- 9. Residence in skilled nursing facility. 10. Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.
- 11. Investigational amyloid lowering therapies are prohibited two months prior to screening and for the duration of the trial. Other investigational agents are prohibited one month prior to screening and for the duration of the trial.
- 12. Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.
- 13. Current use (within 30 days of screening and throughout the protocol including the 2 week follow-up period) of the following medications: a) strong CYP3A4 inhibitors including: atazanavir, indinavir, ritonavir, saquinavir, nelfinavir, ketoconazole, itraconazole, clarithromycin, telithromycin, and nefazodone; b) strong CYP3A4 including: rifampicin, phenytoin, phenobarbital, and carbamazepine; c) certain CYP3A4 substrates including colchicine, cyclosporine, disopyramide, fluticasone, quinidine, vinblastine, vincristine. Patients taking sildenafil, tadalafil, and vardenafil will be advised to stop taking these medications for the duration of the trial.
- 14. Neutropenia defined as absolute neutrophils count of <1,500/microliter. 15. Thrombocytopenia defined as platelet count <100x103/microliter. 16. Current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening.
- 17. Clinically significant abnormalities in screening laboratories, including Aspartate aminotransferase (AST) >1.5 times ULN; Alanine aminotransferase (ALT) > 1.5 times ULN; Total bilirubin >1.5 times ULN; Serum creatinine >2.0 times ULN.
- 18. History of interstitial lung disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Alzheimer's Disease Research Unit
New Haven, Connecticut, 06510
About this study
Official title: A Phase Ib Multiple Ascending Dose Study of the Safety, Tolerability, and CNS Availability of AZD0530 in Alzheimer's Disease
Alzheimer's disease is a devastating neurodegenerative disorder, for which there is currently no effective treatment to slow or halt progression. Beta amyloid peptide accumulates in the brains of those with Alzheimer's, and is thought to play a major role in triggering the dementia. The investigators recently characterized a molecular pathway by which ß-amyloid damages neurons, and showed that the protein termed Fyn kinase is crucial. Our data suggest that blocking Fyn will have a significant therapeutic benefit for Alzheimer's. Astra Zeneca has developed a blocker of Fyn and related kinases (AZD0530) for the treatment of cancer. Chronic AZD0530 administration is well tolerated in humans, and the investigators propose to test its potential as a novel Alzheimer's disease modifying therapy. This study will assess the safety and tolerability of AZD0530 in patients with Alzheimer's disease.
- Conditions
- Alzheimer's Disease
- Being tested
- saracatinib, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
saracatinibDrug
Also called AZD0530
oral drug given to experimental group
PlaceboDrug
Placebo given to placebo group
| Study group | Role | What they receive |
|---|---|---|
| Saracatinib group 1 | Experimental | This group will receive AZD0530 (saracatinib) experimental oral drug , once daily, for a duration of 4 weeks. Dosage is 50mg per day. Receives: Drug: saracatinib |
| Saracatinib group 2 | Experimental | Group 2 will receive saracatinib at a daily oral dose determined by the response to 50mg P.O. daily. Duration is 4 weeks. Receives: Drug: saracatinib |
| Saracatinib group 3 | Experimental | Group 3 will receive saracatinib at a dose determined by the response to 50mg P.O. daily, as well as dose given to group 2. Duration is 4 weeks. Receives: Drug: saracatinib |
| Placebo group 1-3 | Placebo comparator | Subjects receiving saracatinib in groups 1-3 will be compared to subjects receiving daily, oral, placebo drug. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events on AZD0530
Patients will be followed closely for any adverse events. These include laboratory measurements, such as complete blood cell counts, basic metabolic panel, including renal function and electrolyte levels, coagulations factors, and liver function tests. These measures will be assessed weekly. Patients will have cognitive testing weekly, to ensure the absence of a prominent decline in function while on study drug. General daily function will be assessed, and any clinical symptoms, such as dizziness, headache or other symptoms will be addressed. All measures will be compared to baseline testing before drug therapy is started.
Measured: up to 4 weeks
CNS availability of AZD0530 after oral dosing
Cerebrospinal fluid will be obtained at the end of the study to measure drug level. CSF will be obtained by a lumbar puncture.
Measured: 4 weeks
Secondary outcomes (2)
Effects of AZD0530 on cognitive function in patients with Alzheimer's disease
Study participants will undergo a standard cognitive battery, including the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study - Activities of Daily living Inventory (ADCS-ADL), Clinical Dementia Rating - Sum of Boxes (CDR-SOB), Neuropsychiatric Inventory (NPI), and Mini-Mental State Examination (MMSE) at baseline, and at the conclusion of the study. Standard scores from the baseline test battery will be compared to the results at the end of the study to assess any change as a consequence of drug therapy.
Measured: 4 weeks
Effect of AZD0530 on brain glucose metabolism in patients with Alzheimer's disease
A brain FDG-PET scan will be obtained at baseline, and again at the end of the study. Brain glucose metabolism will be assessed quantitatively, and the baseline pre-drug scan will be compared to the scan obtained after 4 weeks of drug/placebo therapy.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startJul 2013
- Primary completionMar 2014
- Study completion6 Nov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stephen M. Strittmatter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stephen M. Strittmatter, Yale University
- Investigators
- Haakon B Nygaard, MD, PhD, Principal investigator, Yale UniversityChristopher van Dyck, MD, Principal investigator, Yale UniversityStephen M Strittmatter, MD, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864655
- Sponsor's protocol ID
- 1303011664
- Other IDs
- 1UH2TR000967-01, 1R01NS084911-01
- Status last verified
- Apr 2021
- First submitted
- 8 May 2013
- Last updated
- 23 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease. Alzheimers Res Ther. 2015 Apr 14;7(1):35. doi: 10.1186/s13195-015-0119-0. eCollection 2015.
PubMed 25874001
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Multiple Ascending Dose Study of the Safety, Tolerability, and CNS Availability of AZD0530 in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01864655
- Acronym / sponsor ID
- 1303011664
- Conditions
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Stephen M. StrittmatterUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jul 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- 6 Nov 2014 (actual)
- First posted
- 29 May 2013 (estimated)
- 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.
Alzheimer's disease is a devastating neurodegenerative disorder, for which there is currently no effective treatment to slow or halt progression. Beta amyloid peptide accumulates in the brains of those with Alzheimer's, and is thought to play a major role in triggering the dementia. The investigators recently characterized a molecular pathway by which ß-amyloid damages neurons, and showed that the protein termed Fyn kinase is crucial. Our data suggest that blocking Fyn will have a significant therapeutic benefit for Alzheimer's. Astra Zeneca has developed a blocker of Fyn and related kinases (AZD0530) for the treatment of cancer. Chronic AZD0530 administration is well tolerated in humans, and the investigators propose to test its potential as a novel Alzheimer's disease modifying therapy. This study will assess the safety and tolerability of AZD0530 in patients with Alzheimer's disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saracatinib group 1 | Experimental | Drug: saracatinibThis group will receive AZD0530 (saracatinib) experimental oral drug , once daily, for a duration of 4 weeks. Dosage is 50mg per day. |
| Saracatinib group 2 | Experimental | Drug: saracatinibGroup 2 will receive saracatinib at a daily oral dose determined by the response to 50mg P.O. daily. Duration is 4 weeks. |
| Saracatinib group 3 | Experimental | Drug: saracatinibGroup 3 will receive saracatinib at a dose determined by the response to 50mg P.O. daily, as well as dose given to group 2. Duration is 4 weeks. |
| Placebo group 1-3 | Placebo comparator | Drug: PlaceboSubjects receiving saracatinib in groups 1-3 will be compared to subjects receiving daily, oral, placebo drug. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. NIA-Alzheimer's Association core clinical criteria for probable AD 2. Age between 50-90 (inclusive). 3. MMSE score between 16 and 26 (inclusive) 4. Clinical Dementia Rating = 0.5, 1.0, or 2 5. Stability of permitted medications for 4 weeks. In particular, subjects may:
- Take stable doses of antidepressants (if they are not currently depressed or do not have a history of major depression within the past 1 year).
- Washout from psychoactive medication for at least 4 weeks prior to screening.
- Cholinesterase inhibitors are allowable if stable for 12 weeks prior to screen. 6. Geriatric Depression Scale less than 6. 7. Study partner is available who has frequent contact with the subject (e.g. an average of 8 hours per week or more), and can accompany the subject to all clinic visits for the duration of the protocol.
- 8. Visual and auditory acuity adequate for neuropsychological testing. 9. Good general health with no diseases expected to interfere with the study. 10. Subject is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
Key exclusion criteria (21 listed)
- 7. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results, or the patient's ability to participate in the study.
- 8. Clinically significant abnormalities in B12 or TFTs that might interfere with the study.
- 9. Residence in skilled nursing facility. 10. Current use (within 30 days of screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications, systemic corticosteroids, or medications with significant central anticholinergic activity, etc.). Current use of warfarin.
- 11. Investigational amyloid lowering therapies are prohibited two months prior to screening and for the duration of the trial. Other investigational agents are prohibited one month prior to screening and for the duration of the trial.
- 12. Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.
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 |
|---|---|---|
| saracatinibAlso: AZD0530oral drug given to experimental group | Drug | Saracatinib group 1, Saracatinib group 2, Saracatinib group 3 |
| PlaceboPlacebo given to placebo group | Drug | Placebo group 1-3 |
Primary outcome
Number of Participants with Adverse Events on AZD0530
Time frame: up to 4 weeks
Patients will be followed closely for any adverse events. These include laboratory measurements, such as complete blood cell counts, basic metabolic panel, including renal function and electrolyte levels, coagulations factors, and liver function tests. These measures will be assessed weekly. Patients will have cognitive testing weekly, to ensure the absence of a prominent decline in function while on study drug. General daily function will be assessed, and any clinical symptoms, such as dizziness, headache or other symptoms will be addressed. All measures will be compared to baseline testing before drug therapy is started.
CNS availability of AZD0530 after oral dosing
Time frame: 4 weeks
Cerebrospinal fluid will be obtained at the end of the study to measure drug level. CSF will be obtained by a lumbar puncture.
2 secondary outcomes
Effects of AZD0530 on cognitive function in patients with Alzheimer's disease
Time frame: 4 weeks
Effect of AZD0530 on brain glucose metabolism in patients with Alzheimer's disease
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
- Derived from this study: PubMed 25874001Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH. A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease. Alzheimers Res Ther. 2015 Apr 14;7(1):35. doi: 10.1186/s13195-015-0119-0. eCollection 2015.
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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. This study is not recruiting at the moment.
Haakon B Nygaard, MD, PhD principal investigator
Yale University
Christopher van Dyck, MD principal investigator
Yale University
Stephen M Strittmatter, MD, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing saracatinib in people with Alzheimer's Disease, run by Stephen M. Strittmatter at 1 site in United States.
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 7 inclusion and 21 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: finished, as of the sponsor's last update on 23 Apr 2021. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events on AZD0530 (time frame: up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01864655, which also lists 1 linked publication.
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 23 Apr 2021; AzTrials last refreshed its copy on 8 Nov 2026.