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History of Changes for Study: NCT02244541
Dose Finding and Pharmacokinetic Study of Anavex2-73 in Patients With Mild to Moderate Alzheimer's Disease (ANAVEX)
Latest version (submitted November 26, 2018) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 17, 2014 None (earliest Version on record)
2 October 5, 2014 Arms and Interventions, Study Status, Study Design, Study Description, Study Identification and Eligibility
3 December 16, 2014 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 February 19, 2015 Contacts/Locations and Study Status
5 April 4, 2015 Contacts/Locations and Study Status
6 June 27, 2015 Contacts/Locations and Study Status
7 September 25, 2015 Study Identification, Outcome Measures, Arms and Interventions, Study Description and Study Status
8 February 3, 2016 Recruitment Status, Study Status and Contacts/Locations
9 August 10, 2016 Study Status and Outcome Measures
10 November 26, 2018 Recruitment Status, Study Status and Study Design
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Study NCT02244541
Submitted Date:  September 17, 2014 (v1)

Open or close this module Study Identification
Unique Protocol ID: ANAVEX2-73-002
Brief Title: Dose Finding and Pharmacokinetic Study of Anavex2-73 in Patients With Mild to Moderate Alzheimer's Disease (ANAVEX)
Official Title: Phase IIa 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 6-Month Open Label Follow-Up Period
Secondary IDs:
Open or close this module Study Status
Record Verification: September 2014
Overall Status: Not yet recruiting
Study Start: November 2014
Primary Completion: September 2015 [Anticipated]
Study Completion: February 2016 [Anticipated]
First Submitted: August 31, 2014
First Submitted that
Met QC Criteria:
September 17, 2014
First Posted: September 19, 2014 [Estimate]
Last Update Submitted that
Met QC Criteria:
September 17, 2014
Last Update Posted: September 19, 2014 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Anavex Life Sciences Corp.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary:

This is a Phase IIa study consisting of two parts (PART A and PART B). The first part (PART A) is a simple randomised, open-label, cross-over, adaptive design study lasting for each participant 36 days. This involves two periods: first period where the participants are split into two groups- one receiving oral form, the other intravenous form. Crossover takes place during the second period.

The second part (PART B) is an open-label extension for an additional period of 26 weeks, so as to establish a longer drug effect for the participants who wish to continue on oral daily dose.

The primary objective 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.

Detailed Description:

This is a Phase IIa 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 26 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 26 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.

Open or close this module Conditions
Conditions: Alzheimer's Disease
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Crossover Assignment
Number of Arms: 8
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 32 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Anavex2-73 oral(30mg) crossover IV (3mg)

Oral form of ANAVEX2-73- 30mg Taken on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1.

IV form of ANAVEX2-73 (3mg) Taken day 1 of period 2, and daily from Day 2 to Day 11.

Drug: ANAVEX2-73 Oral 30mg
30mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 3mg
3mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 Oral(30mg) crossover IV(5mg)

Oral form 30mg Taken on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1.

IV form 5mg Taken on day 1 of period 2, and daily from day 2 to day 11.

Drug: ANAVEX2-73 Oral 30mg
30mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 5mg
5mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 oral(50mg) crossover IV(3mg)

Oral form of ANAVEX2-73- 50mg Taken on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1.

IV form of ANAVEX2-73 (3mg) Taken day 1 of period 2, and daily from Day 2 to Day 11

Drug: ANAVEX2-73 Oral 50mg
50mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 3mg
3mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 Oral(50mg) crossover IV(5mg)

Oral form 50mg Taken on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1.

IV form 5mg Taken on day 1 of period 2, and daily from day 2 to day 11.

Drug: ANAVEX2-73 Oral 50mg
50mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 5mg
5mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 IV(3mg) crossover Oral(30mg)
IV form, 3mg Administered Day 1 of period 1, then daily from Day 3 to 13. Oral form, 30mg Taken daily for 11 days after 11-day washout period
Drug: ANAVEX2-73 Oral 30mg
30mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 3mg
3mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 IV(3mg) crossover Oral(50mg)
IV form, 3mg Administered Day 1 of period 1, then daily from Day 3 to 13. Oral form, 50mg Taken daily for 11 days after 11-day washout period
Drug: ANAVEX2-73 Oral 50mg
50mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 3mg
3mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 IV(5mg) crossover Oral(30mg)
IV form, 5mg Administered Day 1 of period 1, then daily from Day 3 to 13. Oral form, 30mg Taken daily for 11 days after 11-day washout period
Drug: ANAVEX2-73 Oral 30mg
30mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 5mg
5mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Experimental: Anavex2-73 IV(5mg) crossover Oral(50mg)
IV form, 5mg Administered Day 1 of period 1, then daily from Day 3 to 13. Oral form, 50mg Taken daily for 11 days after 11-day washout period
Drug: ANAVEX2-73 Oral 50mg
50mg, capsule form taken orally on day 1, Day 3, and daily for further 10 days (12 doses in total) during Period 1, and during Period 2, taken daily for 11 days in total. 11 day wash-out period in between.
Other Names:
  • ANAVEX2-73
Drug: ANAVEX2-73 IV 5mg
5mg, IV on day 1, day 3 to 13 daily during period 1 and during period 2, day 1 and daily from day 2 to day 11.
Other Names:
  • ANAVEX2-73
Open or close this module Outcome Measures
Primary Outcome Measures:
1. To determine maximum tolerated dose of Anavex2-73.
[ Time Frame: 36 Days ]

Secondary Outcome Measures:
1. 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. ]

2. Mini-mental state examination score (MMSE)
[ Time Frame: Baseline, and during the extension period at Week 1, 12 and 26. ]

3. 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 and 26 ]

4. 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 and 26. ]

5. 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 and 26 of the extension period ]

6. Hamilton Psychiatric Rating Scale for Depression (HAM-D) Score
[ Time Frame: Baseline at Period 1 ]

7. Rosen Modified Hachinski Ischemic Score (RM/HIS10)
[ Time Frame: Baseline at period 1 ]

Open or close this module Eligibility
Minimum Age: 55 Years
Maximum Age: 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Diagnosis of Probable AD in accordance with NINCDS-ADRDA criteria.
  2. A brain CT or MRI scan performed within last 12 months from day of screening consistent with the clinical diagnosis of probable AD.
  3. Age from 55 to 85 years inclusive.
  4. MMSE score of 16-28 inclusive.
  5. Rosen Modified Hachinski Ischemic score <=4.
  6. 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.
  7. Fluency in English.
  8. Be able to read, write, speak clearly for the cognitive tests, with eyesight and hearing sufficient to enable completion of the cognitive tests.
  9. Receiving stable doses of medications for the treatment of non-excluded medical conditions for at least 30 days prior to screening.
  10. If a participant is taking donepezil (allowed acetylcholinesterase inhibitor) then the medication must be maintained on a stable dose regimen for at least 90 days prior to screening evaluations. Donepezil dose is limited to 20 mg/day (with 10mg/d being the maximal recommended daily dose in Australia).

Exclusion Criteria:

  1. Dementia other than AD such as AIDS, CJD, LBD, CVD, Progressive Supranuclear Palsy, Multiple cerebral infarcts, or normal pressure hydrocephalus.
  2. Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumour.
  3. 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.
  4. 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.
  5. History of clinically evident stroke or clinically significant carotid or history vertebrobasilar stenosis or plaque.
  6. History of untreated thyroid disorder, Type 1 diabetes, and insulin dependent or uncontrolled Type II diabetes, as determined by the PI .
  7. History of epilepsy or seizures, excluding febrile seizures in childhood.
  8. Weight > 120 kg (264 lbs).
  9. History of clinical hepatic dysfunction.
  10. Clinically significant infection within the last 30 days .
  11. Treatment with immunosuppressive medications within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
  12. Myocardial infarction within the last 2 years.
  13. History of cancer within the last 5 years, with the exception of basal cell carcinoma and non-metastatic squamous cell carcinoma of the skin.
  14. Other clinically significant abnormality on physical, neurological, laboratory, or ECG examination that could compromise the study or be detrimental to the participant.
  15. Hemoglobin < 11 g/dL.
  16. Smoking > 20 cigarettes per day.
  17. History of alcohol or drug dependence or abuse within the last 2 years.
  18. Current use of other cholinesterase inhibitors rivastigmine or galantamine (donepezil allowed), namenda not allowed, anticonvulsant, anti-Parkinson's, anticoagulant, or narcotic medications are also not allowed.
  19. Current use of over-the-counter "memory enhancing supplements or nutraceuticals".
  20. Problems swallowing pills.
  21. Any prior experimental treatment with the study medication.
  22. Any known hypersensitivity to any of the excipients contained in the study drug formulation.
  23. Any other criteria which in the opinion of the Investigator causes the participant not to qualify for the study.
Open or close this module Contacts/Locations
Central Contact Person: Stephen Macfarlane
Email: S.Macfarlane@cgmc.org.au
Study Officials: Stephen Macfarlane
Principal Investigator
Caulfield Hospital
Locations: Australia, Victoria
Caulfield Hospital
Melbourne, Victoria, Australia, 3162
Contact:Contact: Stephen Macfarlane
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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