Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease (NCT NCT00766363)

NCT ID: NCT00766363

Last Updated: 2012-04-20

Results Overview

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)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 49 participants
• Primary outcome timeframe: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
• Results posted on: 2012-04-20

Participant Flow

The recruitment period was from September 2008 to February 2009 at 4 study centers in the US (CA, FL, and 2 in NJ).

61 subjects were screened and 49 subjects were enrolled.

Participant milestones

Measure	EVP-6124 (0.1 mg/Day) 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
Overall Study PK POPULATION	12	13	10	13
Overall Study COMPLETED	11	12	12	12
Overall Study STARTED	12	13	12	12
Overall Study SAFETY POPULATION	12	13	11	13
Overall Study NOT COMPLETED	1	1	0	0

Reasons for withdrawal

Measure	EVP-6124 (0.1 mg/Day) 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
Overall Study Withdrawal by Subject	1	0	0	0
Overall Study Adverse Event Prior to Randomization	0	1	0	0

Baseline Characteristics

Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease

Baseline characteristics by cohort

Measure	EVP-6124 (0.1 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=11 Participants 1 capsule per day for 28 days.	Placebo n=13 Participants 1 capsule per day for 28 days.	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	18 Participants n=21 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	31 Participants n=21 Participants
Age Continuous	68.6 years STANDARD_DEVIATION 8.5 • n=5 Participants	68.3 years STANDARD_DEVIATION 11.1 • n=7 Participants	70.2 years STANDARD_DEVIATION 12.3 • n=5 Participants	72.0 years STANDARD_DEVIATION 10.5 • n=4 Participants	69.8 years STANDARD_DEVIATION 10.4 • n=21 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	29 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Region of Enrollment United States	12 participants n=5 Participants	13 participants n=7 Participants	11 participants n=5 Participants	13 participants n=4 Participants	49 participants n=21 Participants

PRIMARY outcome

Timeframe: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]

Population: Safety Population: All randomized subjects who ingested at least 1 dose of study drug.

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)

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=11 Participants 1 capsule per day for 28 days.	Placebo n=13 Participants 1 capsule per day for 28 days.
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease Serious Adverse Events	0 Participants	0 Participants	0 Participants	0 Participants
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease Non-Serious Adverse Events	2 Participants	3 Participants	4 Participants	4 Participants
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease No Adverse Events Reported	10 Participants	10 Participants	7 Participants	9 Participants

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=10 Participants 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)	0.0715 ng/mL Standard Deviation 0.0121	0.1911 ng/mL Standard Deviation 0.0740	0.6122 ng/mL Standard Deviation 0.1235	—

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=10 Participants 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)	7.70 hours Standard Deviation 3.31	7.94 hours Standard Deviation 3.61	10.72 hours Standard Deviation 6.69	—

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=11 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=7 Participants 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])	1.31 h*ng/mL Standard Deviation 0.23	3.89 h*ng/mL Standard Deviation 0.84	11.44 h*ng/mL Standard Deviation 2.24	—

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=10 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=7 Participants 1 capsule per day for 28 days.	Placebo n=13 Participants 1 capsule per day for 28 days.
Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)	29.5 ng/mL Standard Deviation 15.8	24.7 ng/mL Standard Deviation 19.8	39.2 ng/mL Standard Deviation 26.7	41.9 ng/mL Standard Deviation 19.7

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

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

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=10 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=12 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=7 Participants 1 capsule per day for 28 days.	Placebo n=13 Participants 1 capsule per day for 28 days.
Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)	2.30 hours Standard Deviation 2.65	1.85 hours Standard Deviation 2.15	3.31 hours Standard Deviation 3.01	3.56 hours Standard Deviation 4.02

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters.

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

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=10 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=7 Participants 1 capsule per day for 28 days.	Placebo n=13 Participants 1 capsule per day for 28 days.
Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])	299 h*ng/mL Standard Deviation 179	240 h*ng/mL Standard Deviation 194	345 h*ng/mL Standard Deviation 225	427 h*ng/mL Standard Deviation 233

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)	23.35 ng/mL Standard Deviation 5.16	3.51 ng/mL Standard Deviation 0.37	—	—

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

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

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)	1.00 hours Standard Deviation 0.02	12.12 hours Standard Deviation 15.72	—	—

SECONDARY outcome

Timeframe: 24 hours

Population: PK Population: All safety population subjects who had sufficient plasma concentration data to facilitate calculation of PK parameters. Only 4 subjects took rivastigmine concomitantly.

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

Outcome measures

Measure	EVP-6124 (0.1 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=2 Participants 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) 1 capsule per day for 28 days.	Placebo 1 capsule per day for 28 days.
Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])	143.55 h*ng/mL Standard Deviation 85.52	54.60 h*ng/mL Standard Deviation 6.28	—	—

Adverse Events

EVP-6124 (0.1 mg/Day)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

EVP-6124 (0.3 mg/Day)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

EVP-6124 (1.0 mg/Day)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	EVP-6124 (0.1 mg/Day) n=12 participants at risk 1 capsule per day for 28 days.	EVP-6124 (0.3 mg/Day) n=13 participants at risk 1 capsule per day for 28 days.	EVP-6124 (1.0 mg/Day) n=11 participants at risk 1 capsule per day for 28 days.	Placebo n=13 participants at risk 1 capsule per day for 28 days.
Cardiac disorders Atrial fibrillation	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	9.1% 1/11 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Eye disorders Vision blurred	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Gastrointestinal disorders Constipation	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	18.2% 2/11 • Number of events 2 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Gastrointestinal disorders Flatulence	16.7% 2/12 • Number of events 2 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Gastrointestinal disorders Nausea	16.7% 2/12 • Number of events 2 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Gastrointestinal disorders Vomiting	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	9.1% 1/11 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
General disorders Vessel puncture site pain	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Infections and infestations Upper respiratory tract infection	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	9.1% 1/11 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Nervous system disorders Headache	16.7% 2/12 • Number of events 2 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 2 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Nervous system disorders Somnolence	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Psychiatric disorders Insomnia	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).
Vascular disorders Hypotension	0.00% 0/12 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/13 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	0.00% 0/11 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).	7.7% 1/13 • Number of events 1 • Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).

Additional Information

Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development

EnVivo Pharmaceuticals, Inc.

Phone: 617-225-4264

Email: mgawryl@envivopharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER