Status:
COMPLETED
A Phase 1 (First in Human) Randomized, Double-blind, Placebo-controlled SAD, MAD Study With Oral REM0046127
Lead Sponsor:
reMYND
Collaborating Sponsors:
NeuroScios GmbH
Conditions:
Alzheimer Disease
Eligibility:
All Genders
18-80 years
Phase:
PHASE1
Brief Summary
This is a phase 1 randomized double blind, first in human (FIH) study with the novel oral Alzheimer drug candidate REM0046127, which consists of two main parts, a single ascending dose (SAD) study wit...
Detailed Description
SAD As a baseline, 5 cohorts of 8 young healthy males are foreseen, with a repeat to assess food impact and an additional elderly cohort. Depending on the early FIH findings, the number of cohorts co...
Eligibility Criteria
Inclusion
- SAD/MAD: Young male subjects aged 18 to 45 years (limits included) willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason
- Elderly Cohorts: Elderly male and female (not of childbearing potential) subjects aged 55 to 80 (limits included) willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason.
- Women not of childbearing potential: Clinically significant abnormalities in screening laboratory tests, including:
- Surgically sterile (bilateral tubal ligation, hysterectomy), or
- Postmenopausal with last natural menses greater than 24 months
- Electrocardiogram without clinically significant pathologic abnormalities and with corrected QT interval (cQT) values lesser than 450 ms
- Normotensive as defined by Systolic Blood Pressure ≤ 150 mm Hg. Diastolic Blood Pressure ≤ 90 mm Hg without antihypertensive medication
- Body Mass Index (BMI) between 18 and 30 kg/m2.
- Body weight between 60 and 80 kg, inclusive
- Only for the elderly cohort of the MAD:
- Participants may be taking medication for non-serious chronic diseases, provided that the dose of these concomitant medications has been stable within the previous 2 months
- No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS)
Exclusion
- Women of childbearing potential (WOCBP)
- Failure to perform screening or baseline examinations
- Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound the interpretation of safety observations according to the clinical assessment of the investigator (physician)
- Evidence of active infection requiring antibiotic therapy within 14 days prior to screening
- Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis
- History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin
- Seropositive for human immunodeficiency virus (HIV)
- History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen \[HbsAg\] or anti-Hepatitis C \[Hepatitis C Virus (HCV)\] antibody)
- Clinically significant abnormalities in screening laboratory tests, including:
- Absolute neutrophil count \< 1.4 x109
- Absolute lymphocyte count \< 1.2 x 109
- Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x the upper limit of normal (ULN)
- Lactate Dehydrogenase (LDH) \> 1.5 x ULN
- Total bilirubin level: Out of normal range 0-1.5 mg/dL
- Estimated glomerular filtration rate (eGFR) \< 60 mL/min
- Haemoglobin (Hgb): out of normal range (male: 13,5-18,0 g/dL).
- Haemoglobin (Hgb): out of normal range (female: 12,0-16,0 g/dL)
- Use of an investigational drug within 2 months prior to dosing in this study
- Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or liver disease)
- Chronic kidney disease (defined as the presence of any degree of proteinuria on urine analysis and/or an eGFR of \<60 ml/min using the (Modification of Diet in Renal Disease (MDRD) formula)
- Psychiatric history of current or past psychosis, bi-polar disorder, major depression, or anxiety disorder requiring chronic medication within the past 5 years
- History of substance abuse, including alcohol and nicotine or positive urine drug screen at screening visit
- Any reason or opinion of the investigator that would prevent the subject from participation in the study
- Inability to follow the instructions or an unwillingness to collaborate during the study
- Male subjects with female partner of child-bearing potential who are unwilling or unable to adhere to contraception requirements
- Only for the elderly cohort of the MAD:
- Chronic daily drug intake during the study period:
- Benzodiazepines, neuroleptics or major sedatives
- Antiepileptics
- Centrally active anti-hypertensive drugs (clonidine, l-methyl-DOPA, guanidine, guanfacine, etc.)
- Opioid containing analgesics
- History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years
- Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the volunteer or put the volunteer at special risk, such as:
- Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (Alanine-Aminotransferase (ALT), Aspartate-Aminotransferase (AST), Gamma Glutamyl-Transferase (GT), alkaline phosphatase \> 2.0 ULN)
- Respiratory insufficiency
- Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening)
- Bradycardia (heartbeat \<50/min) or tachycardia (heartbeat \>95/min)
- Hypertension (\<180/95) or hypotension requiring treatment with more than 2 drugs
- Atrioventricular (AV) block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcF-interval (males \>450 and females \>470 ms)
- Uncontrolled diabetes defined by HbA1c \>8.5
- Renal insufficiency (serum creatinine \> 2mg/dL) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula).
Key Trial Info
Start Date :
November 9 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 26 2022
Estimated Enrollment :
77 Patients enrolled
Trial Details
Trial ID
NCT04672135
Start Date
November 9 2020
End Date
April 26 2022
Last Update
May 19 2022
Active Locations (1)
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1
Medical University Vienna, Department of Clinical Pharmacology
Vienna, Austria, 1090