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 )

Tracking Information

• First Submitted Date: August 18, 2015
• First Posted Date: October 15, 2015
• Results First Submitted Date: March 9, 2017
• Results First Posted Date: May 25, 2017
• Last Update Posted Date: August 11, 2017
• Actual Study Start Date: August 10, 2015
• Actual Primary Completion Date: March 11, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2017)

Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths [ Time Frame: 13 weeks ]

Safety monitoring was conducted throughout the study.

Original Primary Outcome Measures (submitted: October 13, 2015)

Number of patients with adverse events, serious adverse events and deaths [ Time Frame: Date of enrollment until about 30 days after last dose ]

Adverse event and will be evaluated with respect to multiple aspects including incidence, time course, severity, relationship to drug intake etc. Other safety data will be primarily evaluated with respect to out-of-range values and trends over time

Current Secondary Outcome Measures (submitted: April 20, 2017)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Summary of Plasma PK Parameter: Racc [ Time Frame: Day 91 ]
  Racc = the accumulation ratio . Blood samples were collected to assess Racc.
• 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.
• Area-under-plasma Concentration Time Curve up to Infinity (AUCinf) [ Time Frame: Day 91 ]
  CNP520 concentrations in plasma
• Apparent Volume of Distribution (Vz/F) [ Time Frame: Day 91 ]

Original Secondary Outcome Measures (submitted: October 13, 2015)

• Change from baseline of Aβ, Aβ 1-40 and Aβ 1-42 concentrations in CSF [ Time Frame: Predose through study completion (6months) ]
  Change from baseline of Aβ concentrations in CSF
• CNP520 concentrations in CSF [ Time Frame: Predose through study completion (6months) ]
  This outcome measures the CNP520 concentrations in CSF
• Peak plasma concentration (Cmax) [ Time Frame: Predose through study completion (6months) ]
  CNP520 concentrations in plasma
• Area-under-plasma concentration time curve up to infinity (AUCinf) [ Time Frame: Predose through study completion (6months) ]
  CNP520 concentrations in plasma
• Area-under-plasma concentration time curve during dosing interval (AUCtau) [ Time Frame: Predose through study completion (6months) ]
  CNP520 concentrations in plasma
• Terminal elimination half-life (T1/2) [ Time Frame: Predose through study completion (6months) ]
  CNP520 concentrations in plasma
• Apparent volume of distribution (Vz/F) [ Time Frame: Predose through study completion (6months) ]
• Apparent oral clearance (Cl/F) [ Time Frame: Predose through study completion (6months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose-ranging Safety and Tolerability Study in Subjects ≥60 Years of Age
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Alzheimer's Disease

Intervention

• Drug: CNP520
  Other Name: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
• Drug: Placebo
  Matching placebo to CNP520 was supplied in capsules.

Study Arms

• Placebo Comparator: Placebo
  Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.
  Intervention: Drug: Placebo
• Experimental: CNP520 2 mg
  CNP520 2 mg was taken qd orally for 13 weeks.
  Intervention: Drug: CNP520
• Experimental: CNP520 10 mg
  CNP520 10 mg was taken qd orally for 13 weeks.
  Intervention: Drug: CNP520
• Experimental: CNP520 35 mg
  CNP520 35 mg was taken qd orally for 13 weeks.
  Intervention: Drug: CNP520
• Experimental: CNP520 85 mg
  CNP520 85 mg was taken qd orally for 13 weeks.
  Intervention: Drug: CNP520

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 20, 2017): 124
• Original Estimated Enrollment (submitted: October 13, 2015): 125
• Actual Study Completion Date: March 11, 2016
• Actual Primary Completion Date: March 11, 2016 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Germany, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT02576639
• Other Study ID Numbers: CCNP520X2102; 2013-005576-18 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: August 2017