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EUCTR2012-005542-38

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

Datenbasis: WHO (Import vom 15.04.2018)
Geändert: 15.04.2018
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

prodromal Alzheimer's Disease
MedDRA version: 20.0Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 100000004852;Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
In order to be eligible for participation in this trial, the subject must:
1. Be = 50 and = 85 years of age at the Screening Visit.
Meet the following criteria (2-5) for a diagnosis of prodromal AD
2. 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.
3. 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 RBANS (Repeatable Battery for the Assessment of Neuropsychological Status). To meet this criterion, 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 10-30% of the total number randomized).
4. 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 NINCDS-ADRDA criteria).
5. Each subject must have a positive amyloid imaging PET scan using [18F]flutemetamol 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.)
*Subjects with a prior positive amyloid imaging PET scan or a Screening PET scan with florbetaben or florbetapir may be enrolled without a Screening flutemetamol scan with Sponsor approval (see Section 7.1.2.5.7).
6. Have an MMSE score = 24 at Screening.
7. 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.
8. If receiving an acetylcholinesterase inhibitor, memantine, medical food/supplement (e.g., vitamin E), 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 to ensure subject safety. 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 Section 5.5.2 for additional details regarding use of other AD therapy.)
9. 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 (or more in accordance with local requirements), be willing to accompany the subject to all required 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 tri
Exclusion criteria:
1. Has a Rosen-modified Hachinski Ischemia Score > 4 at Screening (i.e., evidence of vascular dementia).
2. Has a known history of stroke or evidence from screening imaging scan (e.g., MRI or CT) that is clinically important in the investigator's opinion.
3. Meets the criteria for a diagnosis of AD dementia, including probable or possible AD, based on DSM-IV-TR or NINCDS-ADRDA [21] criteria at Screening or Baseline.
4. 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.
5. 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 remiss ion is not exclusionary.
6. 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.
7. Has an MRI scan obtained at Screening that shows evidence of a neurological disorder other than prodromal AD or:
- evidence of a prior macrohemorrhage,
- symptomatic vasogenic edema in the investigator´s judgment,
- > 3 lacunar infarcts over 10 mm each, or
- any other clinically significant finding that may account for their cognitive impairment, including but not limited to: brain tumor, large or strategically located cortical or subcortical infarct, or severe white matter disease equaling a rating of 3 on the age-related white matter changes (ARWMC) scale.
8. Has a history of hepatitis or liver disease that, in the opinion of the investigator, has
been active within the six months prior Screening.
9. 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 treated (as documented by repeat urinalysis) prior to baseline.
10. Has a history or current evidence of long QT syndrome, QTC interval 470 milliseconds (for male subjects) or = 480 milliseconds (for female s

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

22.01.2016

Einschluss der ersten teilnehmenden Person

29.04.2016

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

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). - An Efficacy and Safety Trial of MK-8931 (SCH 900931) in Subjects with Prodromal AD (APECS)

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 CDR-SB score at Week 104.;Timepoint(s) of evaluation of this end point: Baseline and 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 CCS-3D
- the change from Baseline at Week 104 in total hippocampal volumen
- the change from Baseline at Week 104 in CSF total tau
- the change from Baseline at Week 104 in composite cortical amyloid standard uptake value ratio assessed with amyloid tracer [18F]Flutemetamol using PET imaging
- the change from Baseline at Week 104 in ADCS-ADLMCI score;Timepoint(s) of evaluation of this end point: -progression to probable AD dementia: Weeks 2, 6, 13, 26, 39, 52, 65, 78, 91, 104
-Mean difference in CDR-SB: Weeks 13 and 104
-CCS-3D: Baseline, Week 104
-Total hippocampal volume: Screening, Week 104
-CSF total tau: Screening, Week 104
-Cortical amyloid SUVR: Screening, Week 104
-ADCS-ADLMCI: Screening, Week 104

Kontakt für Auskünfte (Datenquelle: WHO)

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

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Argentina, Australia, Austria, Belgium, Brazil, Canada, Finland, France, Germany, Hungary, Ireland, 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)

Michael F. Egan
One Merck Drive, P.O. Box 100
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
001267305 7678
michael.egan@merck.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Michael F. Egan
One Merck Drive, P.O. Box 100
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
001267305 7678
michael.egan@merck.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

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

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

8931-019;SCH 900931;2012-005542-38-NO