Dose-ranging Safety and Tolerability Study in Subjects ≥60 Years of Age

Study Overview
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Brief Summary
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The study determined the safety of CNP520 in healthy elderly over 3 months. Data relevant for Pharmacokinetic/Pharmacodynamic modeling were obtained in order to define the target dose in subsequent efficacy studies.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of CNP520 in Healthy Elderly Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: CNP520
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy status Body weight: ≥45kg BMI: 18-34 kg/m2 Key Exclusion Criteria: History or presence of any clinically significant disease of any major system organ class. Heavy smoker status History /presence of clinically significant neurological or psychiatric disorders Any medical condition that might lead to or is associated with any cognitive deficit History or presence of severely impaired renal function

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. | Drug: Placebo<br>* Matching placebo to CNP520 was supplied in capsules.<br>|
| Experimental: CNP520 2 mg<br>CNP520 2 mg was taken qd orally for 13 weeks. | Drug: CNP520<br> <br> * Other names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.;|
| Experimental: CNP520 10 mg<br>CNP520 10 mg was taken qd orally for 13 weeks. | Drug: CNP520<br> <br> * Other names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.;|
| Experimental: CNP520 35 mg<br>CNP520 35 mg was taken qd orally for 13 weeks. | Drug: CNP520<br> <br> * Other names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.;|
| Experimental: CNP520 85 mg<br>CNP520 85 mg was taken qd orally for 13 weeks. | Drug: CNP520<br> <br> * Other names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Safety monitoring was conducted throughout the study. | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | CSF samples were collected by lumbar puncture for assessment. | Day 92 | 
| Summary of Plasma PK Parameter: Cmax | Cmax = the observed maximum plasma concentration following drug administration. Blood samples were collected to assess Cmax. The PK analysis set was used for the analysis. | Days 1, 91 | 
| Summary of Plasma PK Parameter: AUCtau | AUCtau = the area under the plasma concentration-time curve from zero to the end of the dosing interval tau. Blood samples were collected to assess AUCtau. | Days 1 and 91 | 
| Summary of Plasma PK Parameter: Tmax | Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax. | Days 1 and 91 | 
| Summary of Plasma PK Parameter: Tlag | Tlag = time delay between drug administration and first observed concentration above the lower limit of quantification (LOQ) in plasma . Blood samples were collected to assess Tlag. | Days 1 and 91 | 
| Summary of Plasma PK Parameter: T1/2 | T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12. | Day 91 | 
| Summary of PK Parameter: CLss/F | CLss/F = the apparent systemic clearance from plasma observed during a dosing interval at steady state following extravascular administration. Blood samples were collected to assess CLss/F. | Day 91 | 
| Summary of Plasma PK Parameter: Racc | Racc = the accumulation ratio . Blood samples were collected to assess Racc. | Day 91 | 
| Summary of CSF PK Concentrations | CSF samples were collected by lumbar puncture for assessment. | Days 1, 14, 28, 42, 56, 70 and 91 | 
| Area-under-plasma Concentration Time Curve up to Infinity (AUCinf) | CNP520 concentrations in plasma | Day 91 | 
| Apparent Volume of Distribution (Vz/F) |  | Day 91 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease,, Amyloid Beta,, cerebrospinal fluid,, beta secretase