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

Phase 2

Completed

• Conditions: Alzheimer's Disease
• Interventions: Drug: Placebo; Drug: CNP520

• Registration Number: NCT02576639
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-08-10
• Study First Submitted: 2015-08-18
• Study First Submitted QC: 2015-10-13
• Study First Posted: 2015-10-15
• Primary Completion: 2016-03-11
• Study Completion: 2016-03-11
• Results First Submitted: 2017-03-09
• Results First Submitted QC: 2017-04-20
• Results First Posted: 2017-05-25
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-07
• Last Update Posted: 2017-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 124

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.
CNP520 10 mg	CNP520	CNP520 10 mg was taken qd orally for 13 weeks.
CNP520 2 mg	CNP520	CNP520 2 mg was taken qd orally for 13 weeks.
CNP520 35 mg	CNP520	CNP520 35 mg was taken qd orally for 13 weeks.
CNP520 85 mg	CNP520	CNP520 85 mg was taken qd orally for 13 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths	13 weeks	Safety monitoring was conducted throughout the study.

Secondary Outcome Measures

Name	Time	Method
Apparent Volume of Distribution (Vz/F)	Day 91
Summary of PK Parameter: CLss/F	Day 91	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.
Summary of Plasma PK Parameter: Racc	Day 91	Racc = the accumulation ratio . Blood samples were collected to assess Racc.
Summary of CSF PK Concentrations	Days 1, 14, 28, 42, 56, 70 and 91	CSF samples were collected by lumbar puncture for assessment.
Summary of Plasma PK Parameter: Cmax	Days 1, 91	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.
Summary of Plasma PK Parameter: Tlag	Days 1 and 91	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.
Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations	Day 92	CSF samples were collected by lumbar puncture for assessment.
Summary of Plasma PK Parameter: AUCtau	Days 1 and 91	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.
Summary of Plasma PK Parameter: Tmax	Days 1 and 91	Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax.
Summary of Plasma PK Parameter: T1/2	Day 91	T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12.
Area-under-plasma Concentration Time Curve up to Infinity (AUCinf)	Day 91	CNP520 concentrations in plasma

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Mid Glamorgan, United Kingdom