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

• ClinicalTrials.gov Identifier: NCT02576639
• Recruitment Status: Completed
• First Posted: October 15, 2015
• Results First Posted: May 25, 2017
• Last Update Posted: August 11, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: CNP520; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: 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
• Actual Study Start Date: August 10, 2015
• Actual Primary Completion Date: March 11, 2016
• Actual Study Completion Date: March 11, 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.	Drug: Placebo; Matching placebo to CNP520 was supplied in capsules.
Experimental: CNP520 2 mg; CNP520 2 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Name: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 10 mg; CNP520 10 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Name: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 35 mg; CNP520 35 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Name: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 85 mg; CNP520 85 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Name: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths [ Time Frame: 13 weeks ]
   Safety monitoring was conducted throughout the study.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

Glendale, California, United States, 91206

Novartis Investigative Site

Long Beach, California, United States, 90806

United States, Florida

Novartis Investigative Site

Miami, Florida, United States, 33126

United States, Nebraska

Novartis Investigative Site

Lincoln, Nebraska, United States, 68502

Belgium

Novartis Investigative Site

Antwerpen, Belgium, 2060

Germany

Novartis Investigative Site

Berlin, Germany, 14050

Netherlands

Novartis Investigative Site

Groningen, GZ, Netherlands, 9713

Novartis Investigative Site

Leiden, Netherlands, 2333 CL

United Kingdom

Novartis Investigative Site

Belfast, Northern Ireland, United Kingdom, BT9 6AD

Novartis Investigative Site

Harrow, United Kingdom, HA1 3UJ

Novartis Investigative Site

Mid Glamorgan, United Kingdom, CF484DR

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Study Director; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02576639
• Other Study ID Numbers: CCNP520X2102; 2013-005576-18 ( EudraCT Number )
• First Posted: October 15, 2015
• Results First Posted: May 25, 2017
• Last Update Posted: August 11, 2017
• Last Verified: August 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Alzheimer's Disease,; Amyloid Beta,; cerebrospinal fluid,; beta secretase

Additional relevant MeSH terms:

Alzheimer Disease; CNP520; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action