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EUCTR2012-005542-38

A Safety and Efficacy Study for Alzheimer's Disease (Prodromal AD)

Datenbasis: WHO (Import vom 09.12.2018)
Geändert: 04.11.2018
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

prodromal Alzheimer's Disease
MedDRA version: 14.1Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 100000004852

Interventions (Datenquelle: WHO)


Product Name: MK-8931
Product Code: MK-8931
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-8931
Current Sponsor code: MK-8931, SCH900931
Other descriptive name: SCH 900931
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: MK-8931
Product Code: MK-8931
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-8931
Current Sponsor code: MK-8931, SCH900931
Other descriptive name: SCH 900931
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Flutemetamol F18
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Flutemetamol
CAS Number: 765922-62-1
Other descriptive name: Flutemetamol F-18
Concentration unit: MBq/ml megabecquerel(s)/millilitre
Concentration type: equal
Concentration number: 150-

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
Each subject must:
• Be = 50 and = 85 years of age at the Screening Visit.
• Meet the following criteria for a diagnosis of prodromal AD:
o Each subject must report a history of subjective memory decline with gradual onset and slow progression for at least one year before Screening, that is either corroborated by an informant who knows the subject well or is documented in medical records.
o Each subject must have objective impairment in episodic memory at Screening that is =1.0 SD below the appropriate population mean as measured by the screening memory test [Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]. An RBANS delayed memory index score of =85 is required for entry. (Note: the proportion of subjects with RBANS delayed memory index scores ranging from 79 to 85 (approximately 1.5 to 1.0 SD below the appropriate population
mean), inclusive, will not exceed 15-30% of the total number randomized).
o Each subject must have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia (based on DSM-IV-TR and NINCDSADRDA criteria).
o Each subject must have a positive amyloid imaging PET scan using [18F]flutametamol at Screening or positive CSF tau:Aß42 ratio at Screening (see Trial Manuals for details). PET is the primary inclusion tool for the trial. Subjects who fail to meet inclusion criteria based on PET but qualify based on CSF will be enrolled in a separate CSF subgroup of the trial. (Refer to Protocol Section 7.1.3.4 for direction regarding initiation of CSF collection in the trial.)
• Have an MMSE score = 24 at Screening.
• Be able to read at a 6th grade level or equivalent, as determined by the investigator, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation.
• If receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement, and/or herbal medications for AD, be on a stable dose for at least the three months before Screening, and the subject must be willing to remain on the same dose for the duration of the trial. The
treatment and dose that the subject is receiving at Screening must not be changed during the trial unless medically necessary. Additional treatments [including herbal medications] for AD that are not specified in the protocol must not be initiated during the trial. The subject and trial partner must agree that they do not plan to discontinue treatment or initiate additional AD treatments during the trial unless medically necessary. (See Protocol Section 5.5.2 for additional details regarding use of other AD therapy.)
• Have a reliable and competent trial partner/informant who must have a close relationship with the subject, have face to face contact at least three days a week for a minimum of six waking hours a week, be willing to accompany the subject to all trial visits, and be willing to monitor
compliance of the administration of the trial medication. The trial partner/informant should understand the nature of the trial and adhere to trial requirements (e.g., dose, visit schedules, receive phone calls, and evaluations).
• Have results of clinical laboratory tests (complete blood count [CBC], blood chemistries, thyroid stimulating hormone [TSH], and urinalysis) within normal limits or clinically acceptable to the investigator at Screening.
• Have results of a physical examination, vital signs, and ECG within normal lim
Exclusion criteria:
The subject must be excluded from participating in the trial if the subject:
• Has a Rosen modified Hachinski Ischemia Score > 4 at Screening (i.e., evidence of vascular dementia).
• Has a known history of stroke or evidence from screening MRI scan that is clinically important in the investigator's opinion.
• Meets the criteria for a diagnosis of dementia, including probable or possible AD, based on DSM IV TR or NINCDS ADRDA criteria at Screening or Baseline.
• Has evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., prodromal AD) at Screening, including but not limited to: vascular dementia, parkinsonism, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, neurosyphilis, dementia with Lewy bodies, other types of dementia, mental retardation, hypoxic cerebral damage, cognitive impairment due to other disorders, or head trauma with loss of consciousness that led to persistent cognitive
deficits.
• Has evidence of a clinically relevant or unstable psychiatric disorder, based on DSM IV TR criteria, including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium. Major depression in remission is not exclusionary.
• Has evidence of a current episode of major depression based on investigator's judgment. A score on the 15-item Geriatric Depression Scale (GDS) of 5 or more requires an assessment by an appropriate health care professional to evaluate for the presence of major depression. Subjects with a score of 5 or more who are not diagnosed with major depression following such an assessment may be included in the trial.
• Has an MRI scan obtained at Screening that shows evidence of a neurological disorder other than prodromal AD or > 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as possible or definite), a single area of superficial
siderosis, evidence of a prior macrohemorrhage, > 3 lacunar infarcts over 10 mm each, any cortical infarct over 10 mm, or any other clinically significant finding (e.g., any lesion that may account for their cognitive impairment, including but not limited to brain tumor, severe white matter disease with a rating of 3 on the age-related white matter changes (ARWMC) scale, arteriovenous malformation, cavernous hemangioma, or any infarct in a strategic subcortical location).
• Has a history of hepatitis or liver disease that, in the opinion of the investigator, has been active within the six months prior Screening.
• Has a recent or ongoing, uncontrolled, clinically significant medical condition within three months of the Screening Visit (such as, but not limited to, diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function with estimated creatinine clearance < 30 mL/min) other than the condition being studied such that, in the judgment of the investigator, participation in the trial would pose a significant medical risk to the subject. Controlled co-morbid conditions
(including diabetes, hypertension, heart disease, etc.) are not exclusionary if stable within three months of the Screening Visit. All concomitant medications, supplements, or other substances must be kept as stable as medically possible during the trial. Note: urinary tract
infections at screening are not exclusionary if adequately t

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005542-38

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2012-005542-38

Weitere Informationen zur Studie

Registrationsdatum der Studie

14.10.2013

Einschluss der ersten teilnehmenden Person

10.01.2014

Rekrutierungsstatus

Not Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

A Phase III, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Clinical Trial to Study the Efficacy and Safety of MK-8931 (SCH 900931) in Subjects with Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease (Prodromal AD). - A Safety and Efficacy Study for Alzheimer's Disease (Prodromal AD)

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 3

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: • To assess the efficacy of two doses of MK-8931 based on overall clinical progression in subjects with prodromal Alzheimer's Disease (AD).
• To assess the safety and tolerability of two doses of MK-8931 in the treatment of subjects with prodromal AD.
;Secondary Objective: • To assess the efficacy of two doses of MK-8931 in slowing clinical decline and disease progression in subjects with prodromal AD.;Primary end point(s): The primary efficacy endpoint is the change from Baseline in the Clinical Dementia Rating Sum of Boxes (CDR SB) score at Week 104.

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): • the time to progression to probable AD dementia
• the mean difference between the last (Week 104) and first (Week 13) postdose timepoint in CDR-SB
• the change from Baseline at Week 104 in the 3-domain composite cognition score (CCS-3D)
• the change from Baseline at Week 104 in total hippocampal volume
• the change from Baseline at Week 104 in CSF total tau
• the change from Baseline at Week 104 in composite cortical amyloid SUVR assessed with amyloid tracer [18F]Flutemetamol using PET imaging
• the change from Baseline at Week 104 in the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (mild cognitive impairment [MCI] version) (ADCS ADLMCI) score

Kontakt für Auskünfte (Datenquelle: WHO)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Finland, France, Germany, Hungary, Italy, Japan, Korea, Netherlands, New Zealand, Norway, Poland, Republic of, Spain, Switzerland, United Kingdom, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Divisione Ricerca Clinica
Via Fratelli Cervi, snc – Centro Direzionale Milano Due – Palazzo Canova
MSD Italia S.r.l.
+390221018402
gcto.italy@merck.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Divisione Ricerca Clinica
Via Fratelli Cervi, snc – Centro Direzionale Milano Due – Palazzo Canova
MSD Italia S.r.l.
+390221018402
gcto.italy@merck.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

MK-8931-019