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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02576639
Collaborator
(none)
124
Enrollment
11
Locations
5
Arms
7
Actual Duration (Months)
11.3
Patients Per Site
1.6
Patients Per Site Per Month

Study Details

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
Phase 2

Study Design

Study Type:
Interventional
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 :
Aug 10, 2015
Actual Primary Completion Date :
Mar 11, 2016
Actual Study Completion Date :
Mar 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 [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 [Day 92]

      CSF samples were collected by lumbar puncture for assessment.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. Summary of Plasma PK Parameter: T1/2 [Day 91]

      T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12.

    7. 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.

    8. Summary of Plasma PK Parameter: Racc [Day 91]

      Racc = the accumulation ratio . Blood samples were collected to assess Racc.

    9. Summary of CSF PK Concentrations [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) [Day 91]

      CNP520 concentrations in plasma

    11. Apparent Volume of Distribution (Vz/F) [Day 91]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Site City State Country Postal Code
    1 Novartis Investigative Site Glendale California United States 91206
    2 Novartis Investigative Site Long Beach California United States 90806
    3 Novartis Investigative Site Miami Florida United States 33126
    4 Novartis Investigative Site Lincoln Nebraska United States 68502
    5 Novartis Investigative Site Antwerpen Belgium 2060
    6 Novartis Investigative Site Berlin Germany 14050
    7 Novartis Investigative Site Groningen GZ Netherlands 9713
    8 Novartis Investigative Site Leiden Netherlands 2333 CL
    9 Novartis Investigative Site Belfast Northern Ireland United Kingdom BT9 6AD
    10 Novartis Investigative Site Harrow United Kingdom HA1 3UJ
    11 Novartis Investigative Site Mid Glamorgan United Kingdom CF484DR

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Study Director, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02576639
    Other Study ID Numbers:
    • CCNP520X2102
    • 2013-005576-18
    First Posted:
    Oct 15, 2015
    Last Update Posted:
    Aug 11, 2017
    Last Verified:
    Aug 1, 2017
    Keywords provided by Novartis Pharmaceuticals
    Alzheimer's Disease,
    Amyloid Beta,
    cerebrospinal fluid,
    beta secretase
    Additional relevant MeSH terms:
    Alzheimer Disease
    CNP520

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants were randomized in a 1:1:1:1:1 ratio to 5 treatment groups: placebo, CNP520 2 mg, CNP520 10 mg, CNP520 35 mg and CNP520 85 mg.
    Arm/Group Title Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Period Title: Overall Study
    STARTED 24 25 25 26 24
    Pharmacodynamic Analysis Set 24 24 25 25 25
    Pharmacokinetic Analysis Set 0 25 25 26 24
    Safety Analysis Set 24 25 25 26 24
    COMPLETED 22 23 23 25 20
    NOT COMPLETED 2 2 2 1 4

    Baseline Characteristics

    Arm/Group Title Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg Total
    Arm/Group Description Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks. Total of all reporting groups
    Overall Participants 24 25 25 26 24 124
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    66.6
    (5.3)
    65.4
    (4.6)
    66.8
    (5.1)
    66.1
    (4.6)
    66.5
    (5.2)
    66.3
    (4.9)
    Sex: Female, Male (Count of Participants)
    Female
    12
    50%
    16
    64%
    13
    52%
    11
    42.3%
    9
    37.5%
    61
    49.2%
    Male
    12
    50%
    9
    36%
    12
    48%
    15
    57.7%
    15
    62.5%
    63
    50.8%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set, which included participants who received at least 1 dose of study drug (CNP520 or placebo), was analyzed.
    Arm/Group Title Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 24 25 25 26 24
    Non-serious AEs
    18
    75%
    19
    76%
    22
    88%
    20
    76.9%
    18
    75%
    Serious AEs
    0
    0%
    0
    0%
    0
    0%
    1
    3.8%
    0
    0%
    Deaths
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations
    Description CSF samples were collected by lumbar puncture for assessment.
    Time Frame Day 92

    Outcome Measure Data

    Analysis Population Description
    The pharmacodynamics (PD) analysis set was analyzed. The PD set included only randomized participants who had available PD data and no protocol deviations with relevant impact on PD data.
    Arm/Group Title Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 21 22 21 23 20
    Aβ 1-38
    -2.34
    (6.969)
    -20.55
    (10.475)
    -62.48
    (6.202)
    -82.93
    (4.378)
    -89.5
    (1.676)
    Aβ 1-40
    -2.64
    (6.598)
    -22.64
    (9.937)
    -62.89
    (6.485)
    -83.16
    (4.227)
    -90.69
    (1.651)
    Aβ 1-42
    -2.58
    (5.189)
    -23.93
    (8.987)
    -64.28
    (6.086)
    -82.35
    (5.474)
    -89.68
    (2.32)
    3. Secondary Outcome
    Title Summary of Plasma PK Parameter: Cmax
    Description 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.
    Time Frame Days 1, 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 25 25 26 24
    Day 1 (n=25,25,26,24)
    4.76
    (2.92)
    21.3
    (6.67)
    75.6
    (23.4)
    163
    (47.4)
    Day 91 (=23,22,24,20)
    16.6
    (5.51)
    81
    (29.2)
    237
    (65.7)
    602
    (150)
    4. Secondary Outcome
    Title Summary of Plasma PK Parameter: AUCtau
    Description 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.
    Time Frame Days 1 and 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 25 25 26 24
    Day 1 (n=25,25,26,24)
    67.1
    (60.7)
    278
    (65.7)
    966
    (214)
    2300
    (479)
    Day 91 (n=23,22,24,20)
    313
    (117)
    1500
    (476)
    4450
    (1090)
    11200
    (3320)
    5. Secondary Outcome
    Title Summary of Plasma PK Parameter: Tmax
    Description Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax.
    Time Frame Days 1 and 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 25 25 26 24
    Day 1 (n=25,25,26,24)
    2.5
    2.5
    2.5
    2.5
    Day 91 (n=23,22,24,20)
    2.5
    2.5
    2.5
    2.5
    6. Secondary Outcome
    Title Summary of Plasma PK Parameter: Tlag
    Description 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.
    Time Frame Days 1 and 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 25 25 26 24
    Day 1 (n=25,25,26,24)
    0.5
    0.5
    0.5
    0
    Day 91 (n=23,22,24,20)
    0
    0
    0
    0
    7. Secondary Outcome
    Title Summary of Plasma PK Parameter: T1/2
    Description T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12.
    Time Frame Day 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 23 22 24 20
    Mean (Standard Deviation) [hour]
    150
    (52.2)
    155
    (40.9)
    155
    (33.9)
    160
    (22)
    8. Secondary Outcome
    Title Summary of PK Parameter: CLss/F
    Description 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.
    Time Frame Day 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 23 22 24 20
    Mean (Standard Deviation) [mL/h]
    7620
    (2620)
    7380
    (2480)
    8460
    (2790)
    8220
    (2270)
    9. Secondary Outcome
    Title Summary of Plasma PK Parameter: Racc
    Description Racc = the accumulation ratio . Blood samples were collected to assess Racc.
    Time Frame Day 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 23 22 24 20
    Mean (Standard Deviation) [ratio]
    5.86
    (2.25)
    5.33
    (1.05)
    4.75
    (1.16)
    5.02
    (1.47)
    10. Secondary Outcome
    Title Summary of CSF PK Concentrations
    Description CSF samples were collected by lumbar puncture for assessment.
    Time Frame Days 1, 14, 28, 42, 56, 70 and 91

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 25 25 26 24
    Day 1 (n=24,25,26,24)
    0
    (0)
    0
    (0)
    0
    (0)
    0
    (0)
    Day 14 (n=3,4,4,4)
    0.166
    (0.103)
    1.07
    (0.225)
    3.82
    (0.868)
    8.13
    (2.7)
    Day 28 (n=5,2,7,5)
    0.303
    (0.0731)
    1.48
    (0.106)
    4.48
    (1.02)
    12
    (4.12)
    Day 42 (n=3,6,5,5)
    0.314
    (0.0715)
    1.52
    (0.6)
    4
    (1.21)
    7.47
    (1.57)
    Day 56 (n=5,5,2,4)
    0.291
    (0.0605)
    1.28
    (0.177)
    5.03
    (2.69)
    8.04
    (5.69)
    Day 70 (n=6,5,6,4)
    0.231
    (0.149)
    1.04
    (0.212)
    4.62
    (0.753)
    8.71
    (0.71)
    Day 91 (n=23,21,24,20)
    0.305
    (0.099)
    1.44
    (0.431)
    4.52
    (0.946)
    10.4
    (3.26)
    11. Secondary Outcome
    Title Area-under-plasma Concentration Time Curve up to Infinity (AUCinf)
    Description CNP520 concentrations in plasma
    Time Frame Day 91

    Outcome Measure Data

    Analysis Population Description
    This PK parameter was not analyzed because data was not collected.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 0 0 0 0
    12. Secondary Outcome
    Title Apparent Volume of Distribution (Vz/F)
    Description
    Time Frame Day 91

    Outcome Measure Data

    Analysis Population Description
    This PK parameter was not analyzed because data was not collected.
    Arm/Group Title CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Arm/Group Description CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    Measure Participants 0 0 0 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Arm/Group Description Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. CNP520 2 mg was taken qd orally for 13 weeks. CNP520 10 mg was taken qd orally for 13 weeks. CNP520 35 mg was taken qd orally for 13 weeks. CNP520 85 mg was taken qd orally for 13 weeks.
    All Cause Mortality
    Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 18/24 (75%) 19/25 (76%) 22/25 (88%) 20/26 (76.9%) 18/24 (75%)
    Blood and lymphatic system disorders
    Iron deficiency anaemia 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Ear and labyrinth disorders
    Ear discomfort 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Ear pain 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Eustachian tube dysfunction 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Tinnitus 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Eye disorders
    Asthenopia 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Dry eye 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Eye irritation 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Eye pain 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Eye pruritus 0/24 (0%) 0/25 (0%) 2/25 (8%) 0/26 (0%) 1/24 (4.2%)
    Lacrimation increased 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Ocular hyperaemia 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Vision blurred 1/24 (4.2%) 1/25 (4%) 2/25 (8%) 0/26 (0%) 1/24 (4.2%)
    Visual impairment 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Abdominal pain 2/24 (8.3%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Abdominal pain upper 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Constipation 0/24 (0%) 1/25 (4%) 1/25 (4%) 2/26 (7.7%) 1/24 (4.2%)
    Diarrhoea 5/24 (20.8%) 1/25 (4%) 3/25 (12%) 1/26 (3.8%) 1/24 (4.2%)
    Dry mouth 1/24 (4.2%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Dyspepsia 0/24 (0%) 1/25 (4%) 2/25 (8%) 1/26 (3.8%) 0/24 (0%)
    Eructation 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Faeces hard 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Faeces soft 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Flatulence 1/24 (4.2%) 1/25 (4%) 3/25 (12%) 1/26 (3.8%) 0/24 (0%)
    Frequent bowel movements 1/24 (4.2%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Gastrooesophageal reflux disease 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Glossodynia 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Nausea 2/24 (8.3%) 2/25 (8%) 3/25 (12%) 2/26 (7.7%) 2/24 (8.3%)
    Toothache 1/24 (4.2%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 1/24 (4.2%)
    Vomiting 1/24 (4.2%) 2/25 (8%) 0/25 (0%) 2/26 (7.7%) 0/24 (0%)
    General disorders
    Asthenia 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Fatigue 3/24 (12.5%) 0/25 (0%) 0/25 (0%) 2/26 (7.7%) 2/24 (8.3%)
    Feeling cold 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Influenza like illness 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 1/24 (4.2%)
    Injection site pain 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 2/24 (8.3%)
    Pain 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Puncture site pain 0/24 (0%) 1/25 (4%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Vessel puncture site haemorrhage 1/24 (4.2%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Vessel puncture site pain 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Vessel puncture site swelling 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Immune system disorders
    Allergy to chemicals 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Infections and infestations
    Abscess 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Abscess jaw 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Bronchitis 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Hordeolum 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Nasopharyngitis 4/24 (16.7%) 2/25 (8%) 5/25 (20%) 4/26 (15.4%) 1/24 (4.2%)
    Oral herpes 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Rhinitis 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Sinusitis 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Tinea pedis 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Upper respiratory tract infection 2/24 (8.3%) 1/25 (4%) 2/25 (8%) 1/26 (3.8%) 0/24 (0%)
    Urinary tract infection 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Contusion 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Ear abrasion 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Foreign body in eye 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Joint dislocation 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Laceration 1/24 (4.2%) 0/25 (0%) 1/25 (4%) 2/26 (7.7%) 1/24 (4.2%)
    Ligament sprain 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Limb injury 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Post lumbar puncture syndrome 8/24 (33.3%) 2/25 (8%) 1/25 (4%) 3/26 (11.5%) 3/24 (12.5%)
    Post procedural discomfort 0/24 (0%) 0/25 (0%) 2/25 (8%) 1/26 (3.8%) 0/24 (0%)
    Post procedural haemorrhage 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Procedural complication 1/24 (4.2%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Procedural dizziness 2/24 (8.3%) 0/25 (0%) 3/25 (12%) 2/26 (7.7%) 0/24 (0%)
    Procedural nausea 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 1/24 (4.2%)
    Procedural pain 1/24 (4.2%) 3/25 (12%) 4/25 (16%) 2/26 (7.7%) 3/24 (12.5%)
    Scratch 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Skin abrasion 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Thermal burn 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Traumatic lumbar puncture 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Wound complication 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Investigations
    Amylase increased 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Blood bilirubin increased 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Blood cholesterol increased 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Blood creatine phosphokinase increased 0/24 (0%) 2/25 (8%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Blood triglycerides increased 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Gamma-glutamyltransferase increased 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Lipase increased 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Weight decreased 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Metabolism and nutrition disorders
    Gout 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Increased appetite 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/24 (4.2%) 2/25 (8%) 3/25 (12%) 3/26 (11.5%) 1/24 (4.2%)
    Back pain 6/24 (25%) 2/25 (8%) 2/25 (8%) 3/26 (11.5%) 4/24 (16.7%)
    Joint stiffness 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Joint swelling 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Muscle spasms 0/24 (0%) 0/25 (0%) 2/25 (8%) 0/26 (0%) 0/24 (0%)
    Muscle tightness 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Muscular weakness 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Musculoskeletal discomfort 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Musculoskeletal pain 0/24 (0%) 2/25 (8%) 1/25 (4%) 1/26 (3.8%) 1/24 (4.2%)
    Musculoskeletal stiffness 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 2/24 (8.3%)
    Myalgia 3/24 (12.5%) 0/25 (0%) 0/25 (0%) 2/26 (7.7%) 1/24 (4.2%)
    Neck pain 1/24 (4.2%) 2/25 (8%) 0/25 (0%) 1/26 (3.8%) 1/24 (4.2%)
    Pain in extremity 2/24 (8.3%) 2/25 (8%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Plantar fasciitis 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Seborrhoeic keratosis 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Nervous system disorders
    Amnesia 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Balance disorder 0/24 (0%) 1/25 (4%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Cognitive disorder 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Dizziness 3/24 (12.5%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Dizziness postural 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Dysarthria 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Dysgeusia 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Head discomfort 1/24 (4.2%) 1/25 (4%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Headache 10/24 (41.7%) 11/25 (44%) 5/25 (20%) 5/26 (19.2%) 5/24 (20.8%)
    Lethargy 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Neuropathy peripheral 0/24 (0%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Presyncope 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Sedation 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Sinus headache 0/24 (0%) 1/25 (4%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Somnolence 1/24 (4.2%) 1/25 (4%) 0/25 (0%) 2/26 (7.7%) 1/24 (4.2%)
    Syncope 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Tension headache 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Visual field defect 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Psychiatric disorders
    Abnormal dreams 0/24 (0%) 1/25 (4%) 1/25 (4%) 1/26 (3.8%) 1/24 (4.2%)
    Affective disorder 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Confusional state 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Irritability 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Libido decreased 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Nightmare 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Obsessive thoughts 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Renal and urinary disorders
    Micturition urgency 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Pollakiuria 0/24 (0%) 0/25 (0%) 0/25 (0%) 2/26 (7.7%) 1/24 (4.2%)
    Polyuria 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Erectile dysfunction 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Pruritus genital 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 1/24 (4.2%) 2/25 (8%) 3/25 (12%) 3/26 (11.5%) 3/24 (12.5%)
    Dysphonia 2/24 (8.3%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Dyspnoea 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Epistaxis 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Hiccups 0/24 (0%) 1/25 (4%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Nasal congestion 2/24 (8.3%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 1/24 (4.2%)
    Oropharyngeal pain 4/24 (16.7%) 2/25 (8%) 2/25 (8%) 2/26 (7.7%) 0/24 (0%)
    Productive cough 1/24 (4.2%) 1/25 (4%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Rhinorrhoea 2/24 (8.3%) 0/25 (0%) 2/25 (8%) 1/26 (3.8%) 1/24 (4.2%)
    Sinus congestion 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Throat irritation 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Skin and subcutaneous tissue disorders
    Cold sweat 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Dermatitis 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Dermatitis contact 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Dry skin 1/24 (4.2%) 0/25 (0%) 0/25 (0%) 1/26 (3.8%) 0/24 (0%)
    Ecchymosis 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 2/24 (8.3%)
    Erythema 0/24 (0%) 2/25 (8%) 0/25 (0%) 0/26 (0%) 0/24 (0%)
    Pruritus 0/24 (0%) 0/25 (0%) 3/25 (12%) 0/26 (0%) 0/24 (0%)
    Pruritus generalised 0/24 (0%) 1/25 (4%) 2/25 (8%) 0/26 (0%) 1/24 (4.2%)
    Psoriasis 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Rash 0/24 (0%) 1/25 (4%) 1/25 (4%) 0/26 (0%) 0/24 (0%)
    Rash papular 0/24 (0%) 0/25 (0%) 1/25 (4%) 1/26 (3.8%) 0/24 (0%)
    Rash pruritic 0/24 (0%) 0/25 (0%) 0/25 (0%) 0/26 (0%) 1/24 (4.2%)
    Vascular disorders
    Flushing 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 1/24 (4.2%)
    Hot flush 0/24 (0%) 0/25 (0%) 1/25 (4%) 0/26 (0%) 0/24 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02576639
    Other Study ID Numbers:
    • CCNP520X2102
    • 2013-005576-18
    First Posted:
    Oct 15, 2015
    Last Update Posted:
    Aug 11, 2017
    Last Verified:
    Aug 1, 2017