Mild to Moderate Alzheimer’s Disease MedDRA version: 14.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Code: LND101001
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Not Assigned
Current Sponsor code: LND101001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
Lupin Atlantis Holdings S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female outpatients. 2. Patients with a diagnosis of dementia of the Alzheimer's type according to the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV TR™) criteria and a clinical diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria, 2011 Edition17, of AD and DSM-IV criteria of dementia. 3. Age of 50 to 85 years. 4. Brain MRI study to support the clinical diagnosis of AD within the last 12 months prior to the screening visit or during the screening period. 5. Mild to moderate stage of AD according to a MMSE score of 12 to 22 (inclusive) at the screening visit. 6. Clinical evidence of cognitive decline in the past 6 months (based on clinical assessments and patient history data, including reports from caregivers). 7. Patients who are treatment-naïve, have received treatment for AD in the past or currently receiving treatment for AD (in the latter case, Investigators should find it clinically justifiable to switch treatment, and patients should undergo a minimum adequate washout period of 14 days prior to randomization). 8. The patient, if a female, should: ? Have a FSH value indicating menopause with high reliability, AND ? Have had her last natural menstruation = 12 (or a different period, depending on region) months prior to the screening visit, OR ? Have been surgically sterilized prior to the screening visit, OR ? Have had a hysterectomy with oophorectomy prior to the screening visit. 9. The patient, if a male, should: ? Use two methods of contraception in combination; if his female partner is of childbearing potential; e.g., barrier methods such as condom or occlusive cap (diaphragm or cervical/vault cap) with spermicidal foam/gel/film/cream/suppository. (Failure rates indicate that, when used alone, the diaphragm and condom are not highly effective forms of contraception. Therefore, the use of additional spermicides does confer additional theoretical contraceptive protection. However, spermicides alone are inefficient at preventing pregnancy when the whole ejaculate is spilled. Therefore, spermicides are not a barrier method of contraception and should not be used alone.). This combination of contraceptive methods should be used from the baseline visit to = 3 months after the last dose of study medication, OR ? Have been surgically sterilized prior to the screening visit. ? Should not perform or plan to perform sperm donation from the baseline visit to = 3 months after the last dose of study medication. 10. Have good general health, hydration and nutrition status for participating in this clinical study, as assessed by the Investigator. 11. Ability to swallow capsules. 12. Patient living at home or in long-stay residential or care settings not requiring continuous and extensive nursing care; able to walk independently with or without a walking aid (e.g., cane or walker). 13. Patient has an identified, reliable caregiver (at least every day for a minimum of 1 to 2 hours) who is willing to provide support, ensure compliance, correct storage, preparation and administration of the study medication and ready to accompany the patient to study visits whenever required, as well as to provide information about the patient’s physical and behavioral symptoms and changes. 14. The patient and the caregiver are fluent in the language
Exclusion criteria
Exclusion criteria: 1. Clinical, laboratory or neuro-imaging findings consistent with: ? Other primary degenerative dementia, (dementia with Lewy bodies, Parkinson’s disease with dementia, frontotemporal dementia, Huntington’s disease, Jakob Creutzfeldt disease, Down’s syndrome, etc.) and/or vascular dementia. ? Other central nervous system lesions (hydrocephalus, severe head trauma, tumors, subdural hematomas or other relevant space occupying processes, etc.). ? Other relevant infectious, metabolic or systemic diseases (syphilis, juvenile onset diabetes mellitus, clinically significant vitamin B12, folate or thyroid deficiency, clinically significant serum electrolyte disturbances, etc.) affecting central nervous system. ? Any other significant brain pathology/condition (hypoxia, brain infection, mental retardation) that can compromise the safety of the patient as determined by the Investigator. 2. Any current DSM-IV axis I diagnosis other than dementia of the Alzheimer’s type, specifically schizophrenia, schizoaffective disorder, bipolar disorders or major depressive disorder. 3. Patients with major risk of suicidal tendencies and suicide-related behavior, in particular, non-fatal suicide attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior. 4. The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology. 5. The patient has one or more clinical laboratory test values outside the reference range, based on the blood and urine samples taken at the screening visit, that are of potential risk to the patient’s safety or the patient has, at the screening visit: ? A serum total bilirubin value > 1.5 times the upper limit of normal (ULN). ? A serum alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) value > 2 times the ULN. ? A serum creatinine > 2 mg/dL and creatinine clearance = 60 mL/min according to Cockcroft-Gault formula. 6. The patient has, at the screening visit: ? An abnormal ECG that is, in the Investigator’s opinion, clinically significant. ? A PR interval > 250 ms. ? A QRS interval > 130 ms (if not caused by a bundle branch block). ? A QTcF interval > 450 ms (for males and females) (based on the Fridericia correction where QTcF = QT/RR0.33). ? A history of additional risk factors for Torsade de Points (e.g., heart failure, hypokalemia, family history of long QT syndrome). 7. Any clinically significant, advanced or unstable disease or history of that may interfere with primary or secondary variable evaluations, may bias the assessment of the clinical or mental status of the patient or put the patient at special risk. see protocol for more detail 8. In the judgment of the Investigator, the patient is not considered to be euthyroid. If the patient has a TSH level outside the laboratory established reference range, reflex test from TSH will be utilized to test for T4 to support the diagnosis whether the patient is clinically euthyroid. Patients who were previously diagnosed with hyperthyroidism or hypothyroidism and are receiving treatment should have been treated with a stable dose of thyroid supplement for at least the past 3 months. 9. The patient takes or has taken disallowed recent or concomitant medication within the period specified, or it is anticipated that the patient will require treatment during the study with at least one of the disallowed concomitant medications/treatments during the study. 10. The patient has clinic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of two different doses of LND101001 in improving cognitive function in patients with dementia of the Alzheimer's type in comparison with placebo, using the Alzheimer's Disease Assessment Scale - Cognitive Subscale - 13 (ADAS Cog-13) total score.;Secondary Objective: To evaluate the safety and tolerability of two different doses of LND101001.;Primary end point(s): Primary Efficacy Endpoint: • Mean change from baseline in the ADAS-Cog-13 total score at 90 days. ;Timepoint(s) of evaluation of this end point: At day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: • Mean change from baseline in the following: - ADCS-CGIC at 30, 60 and 90 days. - ADAS-Cog-13 total score at 30 and 60 days. - MMSE at 90 days. - ADCS-ADL at 30, 60 and 90 days. - NPI at 90 days. ;Timepoint(s) of evaluation of this end point: Various timepoints during the study | — |
Countries
Croatia, Czech Republic, Germany, Italy, Lithuania, Poland, Romania, Spain, United Kingdom
Contacts
Public ContactDr. Narendra Maharaj
Lupin Limited
Outcome results
None listed