Alzheimer´s DiseasePhase 1/2NCT00948259
Safety Study of a Glycogen Synthase Kinase 3 (GSK3) Inhibitor in Patients With Alzheimer´s Disease
A Phase 1/2 study testing NP031112 in people with Alzheimer´s Disease, run by Noscira SA at 3 sites in Germany.
Trial summary
The purpose of this study is to evaluate if 4 escalating doses during 20 weeks of NP031112 are safe and tolerated in patients with Alzheimer´s disease. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer´s Disease
- What is being tested?
- NP031112
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 3 sitesGermany
- Study dates
- Dec 2008to Nov 2009
- Phase
- Phase 1/2
- 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 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women (non-childbearing potential) with a diagnosis of probable Alzheimer's disease according to the NINCDS-ADRDA clinical criteria.
- Age 60 - 85 years (patients over 85 years could be included after a previous assessment by the investigator and in agreement with the sponsor)
- MRI or CT-scan assessment within 12 months before baseline corroborating the clinical diagnosis (diffuse brain atrophy predominating in medial temporal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3).
- Mild to moderate stage of Alzheimer's disease according to MMSE 16-26.
- Modified Hachinski ischemic score equal to or below 4.
- Geriatric Depression Scale below or equal 7.
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- Female patients must be either surgically sterilized or at least 1 year postmenopausal (confirmed by FSH >20, for women not surgically sterilized).
- A caregiver/nurse is available and is living in the same household, or interacts with the patient to assure the correct preparation and administration of the study drug to the patient.
- Patients living at home or old people's home.
- General health status acceptable for a participation in a 6 months clinical trial.
- Ability to swallow 100 -150 ml of water suspension.
- No daily-regular/chronic intake of medications acting on central nervous system, immunosuppressants, steroids or non-steroid anti-inflammatory agents except the following allowed treatments:
- SSRIs as antidepressants if they are administered at a stable and well tolerated dose for two months prior to baseline evaluation
- the following drugs at a stable and well tolerated dose to symptomatic treatment of mild behavioral disorder, sleep onset-insomnia or mild depressive mood:
- Risperidon max 1mg/day
- Quetiapin max 25mg/day
- Zolpidem max 10mg in the evening
- Lorazepam max 1mg/day
- Triazolam max 0,25mg/day
- Alprazolam max 1mg/day
- Mirtazapin max 30mg/day
- Hydromorphon max 4mg/day
- Levodopa max 50mg t.i.d as treatment of an age-associated extrapyramidal syndrome or restless-legs-syndrome
- Acetylsalicylic acid max 100mg/day as antiplatelet agent.
- Non-steroid anti-rheumatics as concomitant medication taken per request
- No history of treatment with Warfarin, Digitoxin or Coumarin (including its derivatives) within 1 month prior to baseline. Chronic treatment with heparin s.c. as anticoagulant or digoxin for the treatment of heart disease are allowed.
- Other drugs metabolized by the CYP3A4 with wide therapeutic window are permitted if their dose and regimen are stable and well tolerated for at least 1 month prior to baseline.
- Stable pharmacological treatment of any other chronic condition for at least one month prior to screening.
- Treatment with a stable and well tolerated dose of one of the approved Acetylcholinesterase-Inhibitors (Donepezil, Galantamine or Rivastigmine) for at least 2 months prior to baseline evaluations. Dosage of Acetylcholine-esterase inhibitors should not be increased during the ongoing study.
- No history of treatment with Memantine within 3 months prior to baseline evaluation. Patients with a stable and well tolerated dose of Memantine are not allowed to be included in the study.
- Signed informed consent by patient prior to the initiation of any study specific procedure
Who cannot join
- Failure to perform screening or baseline examinations.
- Hospitalization or change of chronic concomitant medication within 1 month prior to screening period.
- Clinical, laboratory or neuroimaging findings consistent with:
- other primary degenerative dementia, (dementia with Lewy bodies, frontotemporal dementia, Huntington's disease, Jacob-Creutzfeld Disease, Down's syndrome, etc)
- other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
- cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions)
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- other central nervous system diseases (severe head trauma, tumors, subdural haematoma or other space occupying processes, etc.)
- seizure disorder
- other infectious, metabolic or systemic diseases affecting 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-IV diagnosis of active major depression, schizophrenia or bipolar disorder.
- Clinically significant, advanced or unstable disease that may interfere with evaluations that may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
- chronic liver disease, liver function test (LFT) abnormalities or other signs of hepatic insufficiency
- respiratory insufficiency
- renal insufficiency (serum creatinine >2mg/dl and creatinine clearance ≤ 60 mL/min according to Cockgroft-Gault formula).
- heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 6 months before screening)
- bradycardia (heart beat <50/min.) or tachycardia (heart beat >95/min.)
- hypertension or hypotension if not well controlled or unstable for > 2 months prior to baseline.
- 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
- malignant tumors within the last 5 years except skin malignancies (other than melanoma) or indolent prostate cancer
- metastases
- Disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.)
- Women who are fertile and of child bearing potential.
- Anticoagulant treatment with heparin i.v.
- Chronic drug intake of:
- drugs metabolized by the CYP3A4 with narrow therapeutic window (i.e. warfarin, digitoxin, …).
- antidepressants, benzodiazepines, neuroleptics or sedatives except those defined as allowed in the inclusion criterion number 12
- proton-pump inhibitors
- antiepileptics
- anticholinergics
- nootropics
- centrally active anti-hypertensive drugs (clonidine, alpha-methyl dopa, guanidine, guanfacine, …)
- opioid containing analgesics
- non-steroid anti-inflammatory agents (except taken as concomitant medication per request as defined in the inclusion criterion number 12), cortico-steroids or immunosuppressants
- memantine, lithium or other inhibitor of GSK3 enzyme
- Suspected or known drug or alcohol abuse.
- Suspected or known allergy to any components of the study treatments.
- Enrolment in another investigational study or intake of investigational drug within the previous 3 months.
- Any condition which in the opinion of the investigator makes the patient unsuitable for inclusion.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Pharmacologische Studiecentrum Chemnitz
Chemnitz, 09111
Arzneimittelforschung Leipzig GmbH
Leipzig, 0410Y
Studienzentrum PD Dr. Steinwachs
Nuremberg, D- 90402
About this study
Official title: Phase IIa 20 Week Double-blind, Placebo-controlled, Randomized, Escalating Dose Study to Evaluate the Safety and Tolerability of Four Oral Doses of NP031112, a Novel GSK3 Inhibitor, in Mild to Moderate Alzheimer's Disease Patients With Stable Anticholinesterasic Treatment.
The purpose of this study is to evaluate if 4 escalating doses during 20 weeks of NP031112 are safe and tolerated in patients with Alzheimer´s disease.
- Conditions
- Alzheimer´s Disease
- Being tested
- NP031112, Placebo
- Keywords
- safety, GSK inhibitor, Alzheimer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NP031112Drug
Also called tideglusib, NP12
unidose sachets containing dry powder for oral suspension, once daily dosing 400 mg (4 to 20 weeks), 600 mg(4 to 16 weeks),800 mg (6 to 12 weeks), 1000 mg (6 weeks)
PlaceboDrug
unidose sachets containing dry powder for oral suspension, once daily dosing 400 mg (4 to 20 weeks), 600 mg(4 to 16 weeks),800 mg (6 to 12 weeks), 1000 mg (6 weeks)
| Study group | Role | What they receive |
|---|---|---|
| NP031112 | Experimental | Patients will receive 400 mg of NP031112 for 4 weeks, if tolerated, they will receive 600 mg for 4 additional weeks. Patients that tolerate this dose will receive 800 mg for 6 weeks and the patients that tolerate this will escalate to 1000 mg for an additional 6 weeks. Patients that are not eligible for dose escalation will remain on the tolerated dose for the remainder of the study. Receives: Drug: NP031112 |
| Placebo | Placebo comparator | Patients will receive 400 mg for 4 weeks, if tolerated, they will receive 600 mg for 4 additional weeks. Patients that tolerate this will receive 800 mg for 6 weeks and the patients that tolerate this will escalate to 1000 mg for an additional 6 weeks. Patients that are not eligible for escalation will remain on the tolerated dose for the remainder of the study. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rates and severity of clinical adverse events and lab abnormalities for each dose level and placebo
Measured: 20 weeks
Secondary outcomes (1)
Effect of treatment with four doses of NP031112 on cognition and depressive mood
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2009 (estimated)
- Study startDec 2008
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Noscira SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Klaus-Christian Steinwachs, MD, Principal investigator, Studienzentrum PD Dr. SteinwachsManfred Windisch, Ph.D., Study director, JSW Life Sciences GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00948259
- Sponsor's protocol ID
- NP031112-08B03 (CR080901)
- Status last verified
- Nov 2009
- First submitted
- 27 Jul 2009
- Last updated
- 11 Nov 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa 20 Week Double-blind, Placebo-controlled, Randomized, Escalating Dose Study to Evaluate the Safety and Tolerability of Four Oral Doses of NP031112, a Novel GSK3 Inhibitor, in Mild to Moderate Alzheimer's Disease Patients With Stable Anticholinesterasic Treatment.
- ClinicalTrials.gov ID
- NCT00948259
- Acronym / sponsor ID
- NP031112-08B03 (CR080901)
- Conditions
- Alzheimer´s Disease
- Keywords
- safety, GSK inhibitor, Alzheimer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Noscira SAIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 29 Jul 2009 (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.
The purpose of this study is to evaluate if 4 escalating doses during 20 weeks of NP031112 are safe and tolerated in patients with Alzheimer´s disease.
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 |
|---|---|---|
| NP031112 | Experimental | Drug: NP031112Patients will receive 400 mg of NP031112 for 4 weeks, if tolerated, they will receive 600 mg for 4 additional weeks. Patients that tolerate this dose will receive 800 mg for 6 weeks and the patients that tolerate this will escalate to 1000 mg for an additional 6 weeks. Patients that are not eligible for dose escalation will remain on the tolerated dose for the remainder of the study. |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive 400 mg for 4 weeks, if tolerated, they will receive 600 mg for 4 additional weeks. Patients that tolerate this will receive 800 mg for 6 weeks and the patients that tolerate this will escalate to 1000 mg for an additional 6 weeks. Patients that are not eligible for escalation will remain on the tolerated dose for the remainder of the study. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Men and women (non-childbearing potential) with a diagnosis of probable Alzheimer's disease according to the NINCDS-ADRDA clinical criteria.
- Age 60 - 85 years (patients over 85 years could be included after a previous assessment by the investigator and in agreement with the sponsor)
- MRI or CT-scan assessment within 12 months before baseline corroborating the clinical diagnosis (diffuse brain atrophy predominating in medial temporal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3).
- Mild to moderate stage of Alzheimer's disease according to MMSE 16-26.
- Modified Hachinski ischemic score equal to or below 4.
Key exclusion criteria (39 listed)
- Failure to perform screening or baseline examinations.
- Hospitalization or change of chronic concomitant medication within 1 month prior to screening period.
- Clinical, laboratory or neuroimaging findings consistent with:
- A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder.
- Clinically significant, advanced or unstable disease that may interfere with evaluations that may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:
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 |
|---|---|---|
| NP031112Also: tideglusib, NP12unidose sachets containing dry powder for oral suspension, once daily dosing 400 mg (4 to 20 weeks), 600 mg(4 to 16 weeks),800 mg (6 to 12 weeks), 1000 mg (6 weeks) | Drug | NP031112 |
| Placebounidose sachets containing dry powder for oral suspension, once daily dosing 400 mg (4 to 20 weeks), 600 mg(4 to 16 weeks),800 mg (6 to 12 weeks), 1000 mg (6 weeks) | Drug | Placebo |
Primary outcome
Incidence rates and severity of clinical adverse events and lab abnormalities for each dose level and placebo
Time frame: 20 weeks
1 secondary outcome
Effect of treatment with four doses of NP031112 on cognition and depressive mood
Time frame: 20 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 11 Nov 2009.
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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.
Klaus-Christian Steinwachs, MD principal investigator
Studienzentrum PD Dr. Steinwachs
Manfred Windisch, Ph.D. study director
JSW Life Sciences GmbH
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NP031112 in people with Alzheimer´s Disease, run by Noscira SA at 3 sites in Germany.
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 31 inclusion and 39 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 11 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Incidence rates and severity of clinical adverse events and lab abnormalities for each dose level and placebo (time frame: 20 weeks). 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 11 Nov 2009.