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| Name | Class |
|---|---|
| Syneos Health | OTHER |
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This study is being conducted to determine the safety, tolerability, and pharmacokinetics (PK) of three different doses of an investigational medication, EVP-6124, in individuals with mild to moderate Alzheimer's disease who are also taking an Alzheimer's medication (AChEI [acetylcholinesterase inhibitor]: either donepezil or rivastigmine). In addition, PK of AChEI medications will be assessed. Cognitive function will be evaluated on an exploratory basis.
This is a randomized, double-blind, placebo-controlled, Phase 1b safety study of three dose levels of EVP-6124 in subjects with mild or moderate Alzheimer's disease and who are taking an AChEI medication (donepezil or rivastigmine).
Study drug will be supplied as capsules and will be orally administered once daily for a total of 28 days. Eligible subjects will be admitted to an inpatient study unit on Day -2 (two days before the first dose of study drug is administered) and will remain confined to the inpatient study unit for a total of five days. Starting on Day 4, subjects will continue the study in the outpatient setting, with study visits on Days 7, 14, 21, and 28. Safety assessments, PK sampling, and cognitive testing will be performed inpatient and at each study visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EVP-6124 (0.1 mg/day) | Experimental |
| |
| EVP-6124 (0.3 mg/day) | Experimental |
| |
| EVP-6124 (1.0 mg/day) | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EVP-6124 (0.1 mg/day) | Drug | EVP-6124 was administered as one 0.1 mg capsule per day for 28 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease | All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood chemistry/urinalysis) | Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only] |
| Measure | Description | Time Frame |
|---|---|---|
| EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma | 24 hours |
| EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David R. Hassmann, D.O. | Comprehensive Clinical Research | Principal Investigator |
| Beth Safirstein, M.D. | MD Clinical | Principal Investigator |
| Stephen Thein, Ph.D. | Pacific Research Network, Inc. | Principal Investigator |
| Jeffrey Apter, M.D. | Global Medical Institutes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pacific Research Network, Inc. | San Diego | California | 92103 | United States | ||
| MD Clinical |
61 subjects were screened and 49 subjects were enrolled.
The recruitment period was from September 2008 to February 2009 at 4 study centers in the US (CA, FL, and 2 in NJ).
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| ID | Title | Description |
|---|---|---|
| FG000 | EVP-6124 (0.1 mg/Day) | 1 capsule per day for 28 days. |
| FG001 | EVP-6124 (0.3 mg/Day) | 1 capsule per day for 28 days. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| EVP-6124 (0.3 mg/day) | Drug | EVP-6124 was administered as one 0.3 mg capsule every day for 28 days. |
|
| EVP-6124 (1.0 mg/day) | Drug | EVP-6124 was administered as one 1.0 mg capsule every day for 28 days. |
|
| Comparator: Placebo | Drug | Matching placebo was administered as one capsule per day for 28 days. |
|
| Donepezil | Drug | Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study. |
|
| Rivastigmine | Drug | Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose. Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study. |
|
EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma |
| 24 hours |
| EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot | 24 hours |
| Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124 | 24 hours |
| Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) | Donepezil PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124 | 24 hours |
| Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | Donepezil PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for donepezil (parent compound only) after dosing with EVP-6124 | 24 hours |
| Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124 | 24 hours |
| Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) | Rivastigmine PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of rivastigmine in plasma after dosing with EVP-6124 | 24 hours |
| Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | Rivastigmine PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for rivastigmine after dosing with EVP-6124 | 24 hours |
| Hallandale |
| Florida |
| 33009 |
| United States |
| Comprehensive Clinical Research | Berlin | New Jersey | 08009 | United States |
| Global Medical Institutes, LLC | Princeton | New Jersey | 08540 | United States |
| FG002 | EVP-6124 (1.0 mg/Day) | 1 capsule per day for 28 days. |
| FG003 | Placebo | 1 capsule per day for 28 days. |
| SAFETY POPULATION |
|
| PK POPULATION |
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| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | EVP-6124 (0.1 mg/Day) | 1 capsule per day for 28 days. |
| BG001 | EVP-6124 (0.3 mg/Day) | 1 capsule per day for 28 days. |
| BG002 | EVP-6124 (1.0 mg/Day) | 1 capsule per day for 28 days. |
| BG003 | Placebo | 1 capsule per day for 28 days. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease | All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood chemistry/urinalysis) | Safety Population: All randomized subjects who ingested at least 1 dose of study drug. | Posted | Number | Participants | Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only] |
|
|
| |||||||||||||||||||||||||||||||||||
| Secondary | EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | ng/mL | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) | EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | hours | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | h*ng/mL | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | ng/mL | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) | Donepezil PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | hours | 24 hours |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | Donepezil PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for donepezil (parent compound only) after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. | Posted | Mean | Standard Deviation | h*ng/mL | 24 hours |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) | Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly. | Posted | Mean | Standard Deviation | ng/mL | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax) | Rivastigmine PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of rivastigmine in plasma after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly. | Posted | Mean | Standard Deviation | hours | 24 hours |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h]) | Rivastigmine PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for rivastigmine after dosing with EVP-6124 | PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly. | Posted | Mean | Standard Deviation | h*ng/mL | 24 hours |
|
|
Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EVP-6124 (0.1 mg/Day) | 1 capsule per day for 28 days. | 0 | 12 | 2 | 12 | ||
| EG001 | EVP-6124 (0.3 mg/Day) | 1 capsule per day for 28 days. | 0 | 13 | 3 | 13 | ||
| EG002 | EVP-6124 (1.0 mg/Day) | 1 capsule per day for 28 days. | 0 | 11 | 4 | 11 | ||
| EG003 | Placebo | 1 capsule per day for 28 days. | 0 | 13 | 4 | 13 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (11.1) | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (11.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (11.1) | Systematic Assessment |
|
The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted for review. At the sponsor's request, the PI will delete confidential information other than trial data and will delay publication or disclosure for up to 90 days to allow patent filings. The PI agrees that the first publication shall be a joint publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development | EnVivo Pharmaceuticals, Inc. | 617-225-4264 | mgawryl@envivopharma.com |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D002493 | Central Nervous System Diseases |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C573817 | 7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide |
| D000077265 | Donepezil |
| D000068836 | Rivastigmine |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D048448 | Phenylcarbamates |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
|
| Non-Serious Adverse Events |
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| No Adverse Events Reported |
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