Alzheimer's DiseasePhase 1NCT00766363

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

A Phase 1 study testing EVP-6124 (0.1 mg/day), EVP-6124 (0.3 mg/day) and EVP-6124 (1.0 mg/day) in people with Alzheimer's Disease and Central Nervous System Diseases, run by FORUM Pharmaceuticals Inc at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 50 to 90 years
Conditions the study is for: Alzheimer's Disease, Central Nervous System Diseases
What is being tested?: EVP-6124 (0.1 mg/day), EVP-6124 (0.3 mg/day) and EVP-6124 (1.0 mg/day)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 4 sitesUnited States
Study dates: Oct 2008to Mar 2009
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 50 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

male and post-menopausal or surgically sterile female pts
50-90 yrs old, who meet clinical criteria for probable Alzheimer's disease (Mini-Mental State Examination of 18-26; Hachinski Ischemic Score ≤4)
must be taking donepezil or rivastigmine for at least 3 mos.

Who cannot join

Unstable medical condition that is clinically significant in the judgment of the investigator; major organ system dysfunction
Untreated hypothyroidism
Insufficiently controlled diabetes mellitus
Diagnosis of major depression requiring antidepressant medications within the last 5 years
Stroke within 6 months before screening, or concomitant with onset of dementia
Certain concomitant medications

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Comprehensive Clinical Research
Berlin, New Jersey, 08009
MD Clinical
Hallandale, Florida, 33009
Global Medical Institutes, LLC
Princeton, New Jersey, 08540
Pacific Research Network, Inc.
San Diego, California, 92103

Other trials in United States

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Phase 1b Safety Study of Three Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo in Patients With Mild to Moderate Probable Alzheimer's Disease

Read the detailed description

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.

Conditions: Alzheimer's Disease, Central Nervous System Diseases
Being tested: EVP-6124 (0.1 mg/day), EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day), Comparator: Placebo, Donepezil
Keywords: Alzheimer's Disease, Central Nervous System Diseases, Pharmacokinetics, Cognition
Medical subject headings: Alzheimer Disease, Central Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EVP-6124 (0.1 mg/day)Drug
EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.
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: PlaceboDrug
Matching placebo was administered as one capsule per day for 28 days.
DonepezilDrug
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.
RivastigmineDrug
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.

Study groups in NCT00766363
Study group	Role	What they receive
EVP-6124 (0.1 mg/day)	Experimental	Not described Receives: Drug: EVP-6124 (0.1 mg/day); Drug: Donepezil; Drug: Rivastigmine
EVP-6124 (0.3 mg/day)	Experimental	Not described Receives: Drug: EVP-6124 (0.3 mg/day); Drug: Donepezil; Drug: Rivastigmine
EVP-6124 (1.0 mg/day)	Experimental	Not described Receives: Drug: EVP-6124 (1.0 mg/day); Drug: Donepezil; Drug: Rivastigmine
Placebo	Placebo comparator	Not described Receives: Drug: Comparator: Placebo; Drug: Donepezil; Drug: Rivastigmine

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (9)

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
Measured: 24 hours
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2008Mar 2009

First posted3 Oct 2008 (estimated)
Study startOct 2008
Primary completionMar 2009
Study completionMar 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00766363
Sponsor's protocol ID: EVP-6124-007
Status last verified: Apr 2012
First submitted: 1 Oct 2008
Last updated: 20 Apr 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Phase 1b Safety Study of Three Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo in Patients With Mild to Moderate Probable Alzheimer's Disease
ClinicalTrials.gov ID: NCT00766363
Acronym / sponsor ID: EVP-6124-007
Conditions: Alzheimer's Disease, Central Nervous System Diseases
Keywords: Alzheimer's Disease, Central Nervous System Diseases, Pharmacokinetics, Cognition
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: FORUM Pharmaceuticals IncIndustry (pharma, biotech, devices)
Collaborators: Syneos Health
Study start: Oct 2008
Primary completion: Mar 2009 (actual)
Study completion: Mar 2009 (actual)
First posted: 3 Oct 2008 (estimated)
Results: Posted 14 Jul 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
EVP-6124 (0.1 mg/day)	Experimental	Drug: EVP-6124 (0.1 mg/day), Drug: Donepezil, Drug: Rivastigmine
EVP-6124 (0.3 mg/day)	Experimental	Drug: EVP-6124 (0.3 mg/day), Drug: Donepezil, Drug: Rivastigmine
EVP-6124 (1.0 mg/day)	Experimental	Drug: EVP-6124 (1.0 mg/day), Drug: Donepezil, Drug: Rivastigmine
Placebo	Placebo comparator	Drug: Comparator: Placebo, Drug: Donepezil, Drug: Rivastigmine

Who may qualify

Ages: 50 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

male and post-menopausal or surgically sterile female pts
50-90 yrs old, who meet clinical criteria for probable Alzheimer's disease (Mini-Mental State Examination of 18-26; Hachinski Ischemic Score ≤4)
must be taking donepezil or rivastigmine for at least 3 mos.

Key exclusion criteria (6 listed)

Unstable medical condition that is clinically significant in the judgment of the investigator; major organ system dysfunction
Untreated hypothyroidism
Insufficiently controlled diabetes mellitus
Diagnosis of major depression requiring antidepressant medications within the last 5 years
Stroke within 6 months before screening, or concomitant with onset of dementia

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
EVP-6124 (0.1 mg/day)EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.	Drug	EVP-6124 (0.1 mg/day)
EVP-6124 (0.3 mg/day)EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.	Drug	EVP-6124 (0.3 mg/day)
EVP-6124 (1.0 mg/day)EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.	Drug	EVP-6124 (1.0 mg/day)
Comparator: PlaceboMatching placebo was administered as one capsule per day for 28 days.	Drug	Placebo
DonepezilConcomitant 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.	Drug	EVP-6124 (0.1 mg/day), EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day), Placebo
RivastigmineConcomitant 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.	Drug	EVP-6124 (0.1 mg/day), EVP-6124 (0.3 mg/day), EVP-6124 (1.0 mg/day), Placebo

Primary outcome

Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
Time frame: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
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)

9 secondary outcomes

EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time frame: 24 hours
EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time frame: 24 hours
EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time frame: 24 hours
Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time frame: 24 hours
Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time frame: 24 hours
Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time frame: 24 hours
Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time frame: 24 hours
Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time frame: 24 hours
Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time frame: 24 hours

Results and safety

Results posted to the registry on 14 Jul 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
EVP-6124 (0.1 mg/Day)	12	11
EVP-6124 (0.3 mg/Day)	13	12
EVP-6124 (1.0 mg/Day)	12	12
Placebo	12	12

Primary outcome: Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease

Time frame: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]. Number. Unit: Participants

Measure	EVP-6124 (0.1 mg/Day) n = 12	EVP-6124 (0.3 mg/Day) n = 13	EVP-6124 (1.0 mg/Day) n = 11	Placebo n = 13
Serious Adverse Events	0	0	0	0
Non-Serious Adverse Events	2	3	4	4
No Adverse Events Reported	10	10	7	9

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

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from pre-treatment (Day -2) to 7 days after the last dose of study drug (Day 35).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
EVP-6124 (0.1 mg/Day)	0 of 12 (0%)	2 of 12 (16.7%)	Not reported
EVP-6124 (0.3 mg/Day)	0 of 13 (0%)	3 of 13 (23.1%)	Not reported
EVP-6124 (1.0 mg/Day)	0 of 11 (0%)	4 of 11 (36.4%)	Not reported
Placebo	0 of 13 (0%)	4 of 13 (30.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

David R. Hassmann, D.O. principal investigator

Comprehensive Clinical Research

Beth Safirstein, M.D. principal investigator

MD Clinical

Stephen Thein, Ph.D. principal investigator

Pacific Research Network, Inc.

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 6 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 20 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease (time frame: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00766363.

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 20 Apr 2012.