Alzheimer's DiseasePhase 2ANAVEXNCT02244541
Phase 2a Dose Finding, PK/PD and 12 Month Exploratory Efficacy Study of ANAVEX2-73 in Patients With Alzheimer's Disease
A Phase 2 study testing ANAVEX2-73 Oral and ANAVEX2-73 Intravenous in people with Alzheimer's Disease, run by Anavex Life Sciences Corp. at 5 sites in Australia.
Trial summary
The primary objective of this Phase 2a study is to evaluate the maximal tolerated dose of ANAVEX2-73 in patients with AD in a repeated-dose administration scheme, with the secondary objectives being to explore the relationship between dosing regimen and pharmacodynamics efficacy outcomes and to evaluate the… Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- ANAVEX2-73 Oral and ANAVEX2-73 Intravenous
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesAustralia
- Study dates
- Dec 2014to Nov 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria:
- Diagnosis of Probable AD in accordance with NINCDS-ADRDA criteria.
- A brain CT or MRI scan performed within last 12 months from day of screening consistent with the clinical diagnosis of probable AD.
- Age from 55 to 85 years inclusive.
- MMSE score of 16-28 inclusive.
- Rosen Modified Hachinski Ischemic score <=4.
- Community dwelling with caregiver who has regular contact with the subject for at least 10 hours per week and is able to oversee the patient's compliance with study medication and participate in the patient's clinical assessment and is capable of accompanying the participant on all clinic visits.
- Fluency in English.
- Be able to read, write, speak clearly for the cognitive tests, with eyesight and hearing sufficient to enable completion of the cognitive tests.
- Receiving stable doses of medications for the treatment of non-excluded medical conditions for at least 30 days prior to screening.
Main Exclusion Criteria:
- Dementia other than AD such as AIDS, CJD, LBD, CVD, Progressive Supranuclear Palsy, Multiple cerebral infarcts, or normal pressure hydrocephalus.
- Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumour.
- Current presence of a clinically significant major psychiatric disorder according to the criteria of the DSM-IV, or symptom that could affect the participant's ability to complete the study). HAM-D score >12.
- Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
- Any other criteria which in the opinion of the Investigator causes the participant not to qualify for the study.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Australia5 sites
Melbourne Health - The Royal Melbourne Hospital
Melbourne, Victoria, 3050
Austin Health - Heidelberg Repatriation Hospital
Melbourne, Victoria, 3084
Caulfield Hospital
Melbourne, Victoria, 3162
Nucleus Network- Centre for Clinical Studies
Melbourne, Victoria
St. Vincent's Hospital
Melbourne, Victoria
About this study
Official title: Phase 2a Study of ANAVEX2-73 Adaptive-Trial-Design With Repeated Doses, MTD Finding, Pharmacodynamic and Bioavailability Evaluation in Patients With Mild to Moderate Alzheimer's Disease With a 12-Month Open Label Follow-Up Period
The primary objective of this Phase 2a study is to evaluate the maximal tolerated dose of ANAVEX2-73 in patients with AD in a repeated-dose administration scheme, with the secondary objectives being to explore the relationship between dosing regimen and pharmacodynamics efficacy outcomes and to evaluate the bioavailability of the oral form used and to explore the relationship of ANAVEX2-73 as add-on therapy to AD standard of care.
Read the detailed description
This is a Phase 2a study consisting of two parts, PART A and PART B. The first part (PART A) is a simple randomised, open-label, 2-period, cross-over, adaptive design study lasting for each participant up to 36 days.
The second part (PART B) is an open-label extension for an additional period of 52 weeks, so as to establish a longer drug effect for the participants who wish to continue on oral daily dose.
The complete timeline of the study includes the screening assessments within 28 days prior to simple randomisation and initiation of the study. The first administration of study medication will occur after all baseline and screening procedures have been passed (baseline is defined as pre-dosing period timeframe day -28 to day -1). No study procedures will be undertaken until a current informed consent form has been signed by each participant or their respective carer or responsible person.
The design of the first part (PART A) of the study involves two periods, two administration routes and two dose levels: In one period the intravenous (iv) form will be given and in the other period the oral dose will be given. The first period will involve 12 administrations (either oral or iv) and the second period will involve 11 administrations (either oral or iv).
The very first administration in the first period is intended as a full pharmacokinetic (PK) screen over the first 48 hours (Day 1 to Day 3). After that, 11 daily administrations complete the first period (Day 3 to Day 13). After a wash-out period of 11 days, the second period of the study starts, involving again 11 daily administrations. Therefore, the first part (PART A) of the study is scheduled to be completed in 36 days.
The study design asks for 32 participants, 16 males and 16 female participants. All participants have the option to go on to the second part (PART B) of the study, the extended open-label study exploring the cognitive effect of the drug for another 52 weeks where the oral form will be exclusively administered.
Safety and tolerability will be constantly assessed throughout the study, starting from the first dose of study medication.
- Conditions
- Alzheimer's Disease
- Being tested
- ANAVEX2-73 Oral, ANAVEX2-73 Intravenous
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANAVEX2-73 OralDrug
ANAVEX2-73 IntravenousDrug
ANAVEX2-73 OralDrug
30 mg hard gelatin capsule
ANAVEX2-73 OralDrug
50 mg hard gelatin capsule
| Study group | Role | What they receive |
|---|---|---|
| Anavex2-73 oral then the Anavex2-73 intravenous formulation | Experimental | Participants first receive Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days. After a washout period of 11 days they then receive the Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days. Receives: Drug: ANAVEX2-73 Oral; Drug: ANAVEX2-73 Intravenous |
| Anavex2-73 intravenous then the Anavex2-73 oral formulation | Experimental | Participants first receive Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days. After a washout period of 11 days then they receive the Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days. Receives: Drug: ANAVEX2-73 Oral; Drug: ANAVEX2-73 Intravenous |
| Anavex2-73 30 mg oral formulation | Experimental | Participants will receive the 30 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks. Receives: Drug: ANAVEX2-73 Oral |
| Anavex2-73 50 mg oral formulation | Experimental | Participants will receive the 50 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks. Receives: Drug: ANAVEX2-73 Oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine maximum tolerated dose of Anavex2-73.
Measured: 36 Days
Secondary outcomes (7)
PK sampling- blood test results
Measured: First part (PART A), first period (hours): 1, 48, 264; second period (hours): 1, 72, 264; extension period (PART B): Week 1, 12 and 26.
Mini-mental state examination score (MMSE)
Measured: Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52
Score from ADCS-ADL (Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory)
Measured: Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52
Cogstate Brief Battery (CBB) Score and International Shopping List Task (ISLT) Score
Measured: At baseline, Day 1, 2, 6, 9, 12 of Period 1 and Day 1, 2, 6, 9, 12 of Period 2 and during the extension period at Week 12, 36, 48, and 52.
Electroencephalographic activity, including event-related potentials (EEG/ERP)
Measured: baseline, Day 1, 5, 11 of Period 1 and Day 1, 5, 11 of Period 2 and, Week 12, 36, 48, and 52 of the extension period
Hamilton Psychiatric Rating Scale for Depression (HAM-D) Score
Measured: Baseline at Period 1
Rosen Modified Hachinski Ischemic Score (RM/HIS10)
Measured: Baseline at period 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2014 (estimated)
- Study startDec 2014
- Primary completionNov 2015
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anavex Life Sciences Corp.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Macfarlane, Principal investigator, Caulfield Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244541
- Sponsor's protocol ID
- ANAVEX2-73-002
- Acronym
- ANAVEX
- Status last verified
- Nov 2018
- First submitted
- 31 Aug 2014
- Last updated
- 28 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2a Study of ANAVEX2-73 Adaptive-Trial-Design With Repeated Doses, MTD Finding, Pharmacodynamic and Bioavailability Evaluation in Patients With Mild to Moderate Alzheimer's Disease With a 12-Month Open Label Follow-Up Period
- ClinicalTrials.gov ID
- NCT02244541
- Acronym / sponsor ID
- ANAVEX / ANAVEX2-73-002
- Conditions
- Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Anavex Life Sciences Corp.Industry (pharma, biotech, devices)
- Study start
- Dec 2014 (actual)
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 19 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this Phase 2a study is to evaluate the maximal tolerated dose of ANAVEX2-73 in patients with AD in a repeated-dose administration scheme, with the secondary objectives being to explore the relationship between dosing regimen and pharmacodynamics efficacy outcomes and to evaluate the bioavailability of the oral form used and to explore the relationship of ANAVEX2-73 as add-on therapy to AD standard of care.
Detailed description
This is a Phase 2a study consisting of two parts, PART A and PART B. The first part (PART A) is a simple randomised, open-label, 2-period, cross-over, adaptive design study lasting for each participant up to 36 days.
The second part (PART B) is an open-label extension for an additional period of 52 weeks, so as to establish a longer drug effect for the participants who wish to continue on oral daily dose.
The complete timeline of the study includes the screening assessments within 28 days prior to simple randomisation and initiation of the study. The first administration of study medication will occur after all baseline and screening procedures have been passed (baseline is defined as pre-dosing period timeframe day -28 to day -1). No study procedures will be undertaken until a current informed consent form has been signed by each participant or their respective carer or responsible person.
The design of the first part (PART A) of the study involves two periods, two administration routes and two dose levels: In one period the intravenous (iv) form will be given and in the other period the oral dose will be given. The first period will involve 12 administrations (either oral or iv) and the second period will involve 11 administrations (either oral or iv).
The very first administration in the first period is intended as a full pharmacokinetic (PK) screen over the first 48 hours (Day 1 to Day 3). After that, 11 daily administrations complete the first period (Day 3 to Day 13). After a wash-out period of 11 days, the second period of the study starts, involving again 11 daily administrations. Therefore, the first part (PART A) of the study is scheduled to be completed in 36 days.
The study design asks for 32 participants, 16 males and 16 female participants. All participants have the option to go on to the second part (PART B) of the study, the extended open-label study exploring the cognitive effect of the drug for another 52 weeks where the oral form will be exclusively administered.
Safety and tolerability will be constantly assessed throughout the study, starting from the first dose of study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Anavex2-73 oral then the Anavex2-73 intravenous formulation | Experimental | Drug: ANAVEX2-73 Oral, Drug: ANAVEX2-73 IntravenousParticipants first receive Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days. After a washout period of 11 days they then receive the Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days. |
| Anavex2-73 intravenous then the Anavex2-73 oral formulation | Experimental | Drug: ANAVEX2-73 Oral, Drug: ANAVEX2-73 IntravenousParticipants first receive Anavex2-73 intravenous formulation each morning with a light breakfast for 11 days. After a washout period of 11 days then they receive the Anavex2-73 hard gelatin capsule each morning with a light breakfast for 11 days. |
| Anavex2-73 30 mg oral formulation | Experimental | Drug: ANAVEX2-73 OralParticipants will receive the 30 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks. |
| Anavex2-73 50 mg oral formulation | Experimental | Drug: ANAVEX2-73 OralParticipants will receive the 50 mg Anavex2-73 hard gelatin capsule orally once daily for 52 weeks. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| ANAVEX2-73 Oral | Drug | Anavex2-73 intravenous then the Anavex2-73 oral formulation, Anavex2-73 oral then the Anavex2-73 intravenous formulation |
| ANAVEX2-73 Intravenous | Drug | Anavex2-73 intravenous then the Anavex2-73 oral formulation, Anavex2-73 oral then the Anavex2-73 intravenous formulation |
| ANAVEX2-73 Oral30 mg hard gelatin capsule | Drug | Anavex2-73 30 mg oral formulation |
| ANAVEX2-73 Oral50 mg hard gelatin capsule | Drug | Anavex2-73 50 mg oral formulation |
Primary outcome
To determine maximum tolerated dose of Anavex2-73.
Time frame: 36 Days
7 secondary outcomes
PK sampling- blood test results
Time frame: First part (PART A), first period (hours): 1, 48, 264; second period (hours): 1, 72, 264; extension period (PART B): Week 1, 12 and 26.
Mini-mental state examination score (MMSE)
Time frame: Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52
Score from ADCS-ADL (Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory)
Time frame: Baseline, and during the extension period at Week 1, 12, 26, 36, 48, and 52
Cogstate Brief Battery (CBB) Score and International Shopping List Task (ISLT) Score
Time frame: At baseline, Day 1, 2, 6, 9, 12 of Period 1 and Day 1, 2, 6, 9, 12 of Period 2 and during the extension period at Week 12, 36, 48, and 52.
Electroencephalographic activity, including event-related potentials (EEG/ERP)
Time frame: baseline, Day 1, 5, 11 of Period 1 and Day 1, 5, 11 of Period 2 and, Week 12, 36, 48, and 52 of the extension period
Hamilton Psychiatric Rating Scale for Depression (HAM-D) Score
Time frame: Baseline at Period 1
Rosen Modified Hachinski Ischemic Score (RM/HIS10)
Time frame: Baseline at period 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2018.
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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.
Stephen Macfarlane principal investigator
Caulfield Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ANAVEX2-73 Oral and ANAVEX2-73 Intravenous in people with Alzheimer's Disease, run by Anavex Life Sciences Corp. at 5 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 28 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine maximum tolerated dose of Anavex2-73. (time frame: 36 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Nov 2018.