A Phase 1 (First in Human) Randomized, Double-blind, Placebo-controlled SAD, MAD Study With Oral REM0046127

• Status: Recruiting
• Trial end date: 2022-05-30
• Target enrollment: 0
• Participant gender: All

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 with 7 cohorts followed by a multiple ascending dose (MAD) study with 2 cohorts.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: reMYND
• Collaborator: NeuroScios GmbH

Criteria

Inclusion Criteria:

1. 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

2. 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.

3. 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

4. Electrocardiogram without clinically significant pathologic abnormalities and with corrected QT interval (cQT) values lesser than 450 ms

5. Normotensive as defined by Systolic Blood Pressure ≤ 150 mm Hg. Diastolic Blood Pressure ≤ 90 mm Hg without antihypertensive medication

6. Body Mass Index (BMI) between 18 and 30 kg/m2.

7. Body weight between 60 and 80 kg, inclusive

Only for the elderly cohort of the MAD:

8. 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

9. No suicidal ideation, as demonstrated by a score of "0" on the Columbia Suicide Severity Rating Scale (C-SSRS)

Exclusion Criteria:

1. Women of childbearing potential (WOCBP)

2. Failure to perform screening or baseline examinations

3. 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)

4. Evidence of active infection requiring antibiotic therapy within 14 days prior to screening

5. Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis

6. History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin

7. Seropositive for human immunodeficiency virus (HIV)

8. 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)

9. 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)

10. Use of an investigational drug within 2 months prior to dosing in this study

11. 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)

12. 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)

13. Psychiatric history of current or past psychosis, bi-polar disorder, major depression, or anxiety disorder requiring chronic medication within the past 5 years

14. History of substance abuse, including alcohol and nicotine or positive urine drug screen at screening visit

15. Any reason or opinion of the investigator that would prevent the subject from participation in the study

16. Inability to follow the instructions or an unwillingness to collaborate during the study

17. 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:

18. 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

19. 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

20. 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).