Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease,, Amyloid Beta,, cerebrospinal fluid,, beta secretase
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.
Interventions
DRUGCNP520
DRUGPlacebo
Matching placebo to CNP520 was supplied in capsules.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | 13 weeks | Safety monitoring was conducted throughout the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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. |
| Summary of Plasma PK Parameter: T1/2 | Day 91 | T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12. |
| 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: 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. |
| Area-under-plasma Concentration Time Curve up to Infinity (AUCinf) | Day 91 | CNP520 concentrations in plasma |
| 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. |
Countries
Belgium, Germany, Netherlands, United Kingdom, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks. | 24 |
| CNP520 2 mg CNP520 2 mg was taken qd orally for 13 weeks. | 25 |
| CNP520 10 mg CNP520 10 mg was taken qd orally for 13 weeks. | 25 |
| CNP520 35 mg CNP520 35 mg was taken qd orally for 13 weeks. | 26 |
| CNP520 85 mg CNP520 85 mg was taken qd orally for 13 weeks. | 24 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | CNP520 2 mg | CNP520 10 mg | CNP520 35 mg | CNP520 85 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 66.6 Years STANDARD_DEVIATION 5.3 | 65.4 Years STANDARD_DEVIATION 4.6 | 66.8 Years STANDARD_DEVIATION 5.1 | 66.1 Years STANDARD_DEVIATION 4.6 | 66.5 Years STANDARD_DEVIATION 5.2 | 66.3 Years STANDARD_DEVIATION 4.9 |
| Sex: Female, Male Female | 12 Participants | 16 Participants | 13 Participants | 11 Participants | 9 Participants | 61 Participants |
| Sex: Female, Male Male | 12 Participants | 9 Participants | 12 Participants | 15 Participants | 15 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 24 | 19 / 25 | 22 / 25 | 20 / 26 | 18 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 | 0 / 25 | 1 / 26 | 0 / 24 |
Outcome results
Primary
Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths
Safety monitoring was conducted throughout the study.
Time frame: 13 weeks
Population: The safety analysis set, which included participants who received at least 1 dose of study drug (CNP520 or placebo), was analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Serious AEs | 0 Participants |
| Placebo | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Non-serious AEs | 18 Participants |
| Placebo | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Deaths | 0 Participants |
| CNP520 2 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Non-serious AEs | 19 Participants |
| CNP520 2 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Deaths | 0 Participants |
| CNP520 2 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Serious AEs | 0 Participants |
| CNP520 10 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Non-serious AEs | 22 Participants |
| CNP520 10 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Serious AEs | 0 Participants |
| CNP520 10 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Deaths | 0 Participants |
| CNP520 35 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Deaths | 0 Participants |
| CNP520 35 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Non-serious AEs | 20 Participants |
| CNP520 35 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Serious AEs | 1 Participants |
| CNP520 85 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Serious AEs | 0 Participants |
| CNP520 85 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Non-serious AEs | 18 Participants |
| CNP520 85 mg | Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths | Deaths | 0 Participants |
Secondary
Apparent Volume of Distribution (Vz/F)
Time frame: Day 91
Population: This PK parameter was not analyzed because data was not collected.
Secondary
Area-under-plasma Concentration Time Curve up to Infinity (AUCinf)
CNP520 concentrations in plasma
Time frame: Day 91
Population: This PK parameter was not analyzed because data was not collected.
Secondary
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.
Time frame: Day 92
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-38 | -2.34 Percentage change | Standard Deviation 6.969 |
| Placebo | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-42 | -2.58 Percentage change | Standard Deviation 5.189 |
| Placebo | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-40 | -2.64 Percentage change | Standard Deviation 6.598 |
| CNP520 2 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-40 | -22.64 Percentage change | Standard Deviation 9.937 |
| CNP520 2 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-38 | -20.55 Percentage change | Standard Deviation 10.475 |
| CNP520 2 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-42 | -23.93 Percentage change | Standard Deviation 8.987 |
| CNP520 10 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-40 | -62.89 Percentage change | Standard Deviation 6.485 |
| CNP520 10 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-38 | -62.48 Percentage change | Standard Deviation 6.202 |
| CNP520 10 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-42 | -64.28 Percentage change | Standard Deviation 6.086 |
| CNP520 35 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-38 | -82.93 Percentage change | Standard Deviation 4.378 |
| CNP520 35 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-42 | -82.35 Percentage change | Standard Deviation 5.474 |
| CNP520 35 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-40 | -83.16 Percentage change | Standard Deviation 4.227 |
| CNP520 85 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-40 | -90.69 Percentage change | Standard Deviation 1.651 |
| CNP520 85 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-38 | -89.5 Percentage change | Standard Deviation 1.676 |
| CNP520 85 mg | Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations | Aβ 1-42 | -89.68 Percentage change | Standard Deviation 2.32 |
Secondary
Summary of CSF PK Concentrations
CSF samples were collected by lumbar puncture for assessment.
Time frame: Days 1, 14, 28, 42, 56, 70 and 91
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of CSF PK Concentrations | Day 1 (n=24,25,26,24) | 0 ng/mL | Standard Deviation 0 |
| Placebo | Summary of CSF PK Concentrations | Day 70 (n=6,5,6,4) | 0.231 ng/mL | Standard Deviation 0.149 |
| Placebo | Summary of CSF PK Concentrations | Day 56 (n=5,5,2,4) | 0.291 ng/mL | Standard Deviation 0.0605 |
| Placebo | Summary of CSF PK Concentrations | Day 14 (n=3,4,4,4) | 0.166 ng/mL | Standard Deviation 0.103 |
| Placebo | Summary of CSF PK Concentrations | Day 91 (n=23,21,24,20) | 0.305 ng/mL | Standard Deviation 0.099 |
| Placebo | Summary of CSF PK Concentrations | Day 28 (n=5,2,7,5) | 0.303 ng/mL | Standard Deviation 0.0731 |
| Placebo | Summary of CSF PK Concentrations | Day 42 (n=3,6,5,5) | 0.314 ng/mL | Standard Deviation 0.0715 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 70 (n=6,5,6,4) | 1.04 ng/mL | Standard Deviation 0.212 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 42 (n=3,6,5,5) | 1.52 ng/mL | Standard Deviation 0.6 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 28 (n=5,2,7,5) | 1.48 ng/mL | Standard Deviation 0.106 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 56 (n=5,5,2,4) | 1.28 ng/mL | Standard Deviation 0.177 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 91 (n=23,21,24,20) | 1.44 ng/mL | Standard Deviation 0.431 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 14 (n=3,4,4,4) | 1.07 ng/mL | Standard Deviation 0.225 |
| CNP520 2 mg | Summary of CSF PK Concentrations | Day 1 (n=24,25,26,24) | 0 ng/mL | Standard Deviation 0 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 42 (n=3,6,5,5) | 4 ng/mL | Standard Deviation 1.21 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 1 (n=24,25,26,24) | 0 ng/mL | Standard Deviation 0 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 14 (n=3,4,4,4) | 3.82 ng/mL | Standard Deviation 0.868 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 28 (n=5,2,7,5) | 4.48 ng/mL | Standard Deviation 1.02 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 56 (n=5,5,2,4) | 5.03 ng/mL | Standard Deviation 2.69 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 70 (n=6,5,6,4) | 4.62 ng/mL | Standard Deviation 0.753 |
| CNP520 10 mg | Summary of CSF PK Concentrations | Day 91 (n=23,21,24,20) | 4.52 ng/mL | Standard Deviation 0.946 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 28 (n=5,2,7,5) | 12 ng/mL | Standard Deviation 4.12 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 91 (n=23,21,24,20) | 10.4 ng/mL | Standard Deviation 3.26 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 70 (n=6,5,6,4) | 8.71 ng/mL | Standard Deviation 0.71 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 14 (n=3,4,4,4) | 8.13 ng/mL | Standard Deviation 2.7 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 1 (n=24,25,26,24) | 0 ng/mL | Standard Deviation 0 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 56 (n=5,5,2,4) | 8.04 ng/mL | Standard Deviation 5.69 |
| CNP520 35 mg | Summary of CSF PK Concentrations | Day 42 (n=3,6,5,5) | 7.47 ng/mL | Standard Deviation 1.57 |
Secondary
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.
Time frame: Day 91
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Summary of PK Parameter: CLss/F | 7620 mL/h | Standard Deviation 2620 |
| CNP520 2 mg | Summary of PK Parameter: CLss/F | 7380 mL/h | Standard Deviation 2480 |
| CNP520 10 mg | Summary of PK Parameter: CLss/F | 8460 mL/h | Standard Deviation 2790 |
| CNP520 35 mg | Summary of PK Parameter: CLss/F | 8220 mL/h | Standard Deviation 2270 |
Secondary
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.
Time frame: Days 1 and 91
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: AUCtau | Day 1 (n=25,25,26,24) | 67.1 h*ng/mL | Standard Deviation 60.7 |
| Placebo | Summary of Plasma PK Parameter: AUCtau | Day 91 (n=23,22,24,20) | 313 h*ng/mL | Standard Deviation 117 |
| CNP520 2 mg | Summary of Plasma PK Parameter: AUCtau | Day 91 (n=23,22,24,20) | 1500 h*ng/mL | Standard Deviation 476 |
| CNP520 2 mg | Summary of Plasma PK Parameter: AUCtau | Day 1 (n=25,25,26,24) | 278 h*ng/mL | Standard Deviation 65.7 |
| CNP520 10 mg | Summary of Plasma PK Parameter: AUCtau | Day 1 (n=25,25,26,24) | 966 h*ng/mL | Standard Deviation 214 |
| CNP520 10 mg | Summary of Plasma PK Parameter: AUCtau | Day 91 (n=23,22,24,20) | 4450 h*ng/mL | Standard Deviation 1090 |
| CNP520 35 mg | Summary of Plasma PK Parameter: AUCtau | Day 1 (n=25,25,26,24) | 2300 h*ng/mL | Standard Deviation 479 |
| CNP520 35 mg | Summary of Plasma PK Parameter: AUCtau | Day 91 (n=23,22,24,20) | 11200 h*ng/mL | Standard Deviation 3320 |
Secondary
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.
Time frame: Days 1, 91
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: Cmax | Day 1 (n=25,25,26,24) | 4.76 ng/mL | Standard Deviation 2.92 |
| Placebo | Summary of Plasma PK Parameter: Cmax | Day 91 (=23,22,24,20) | 16.6 ng/mL | Standard Deviation 5.51 |
| CNP520 2 mg | Summary of Plasma PK Parameter: Cmax | Day 91 (=23,22,24,20) | 81 ng/mL | Standard Deviation 29.2 |
| CNP520 2 mg | Summary of Plasma PK Parameter: Cmax | Day 1 (n=25,25,26,24) | 21.3 ng/mL | Standard Deviation 6.67 |
| CNP520 10 mg | Summary of Plasma PK Parameter: Cmax | Day 1 (n=25,25,26,24) | 75.6 ng/mL | Standard Deviation 23.4 |
| CNP520 10 mg | Summary of Plasma PK Parameter: Cmax | Day 91 (=23,22,24,20) | 237 ng/mL | Standard Deviation 65.7 |
| CNP520 35 mg | Summary of Plasma PK Parameter: Cmax | Day 1 (n=25,25,26,24) | 163 ng/mL | Standard Deviation 47.4 |
| CNP520 35 mg | Summary of Plasma PK Parameter: Cmax | Day 91 (=23,22,24,20) | 602 ng/mL | Standard Deviation 150 |
Secondary
Summary of Plasma PK Parameter: Racc
Racc = the accumulation ratio . Blood samples were collected to assess Racc.
Time frame: Day 91
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: Racc | 5.86 ratio | Standard Deviation 2.25 |
| CNP520 2 mg | Summary of Plasma PK Parameter: Racc | 5.33 ratio | Standard Deviation 1.05 |
| CNP520 10 mg | Summary of Plasma PK Parameter: Racc | 4.75 ratio | Standard Deviation 1.16 |
| CNP520 35 mg | Summary of Plasma PK Parameter: Racc | 5.02 ratio | Standard Deviation 1.47 |
Secondary
Summary of Plasma PK Parameter: T1/2
T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12.
Time frame: Day 91
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: T1/2 | 150 hour | Standard Deviation 52.2 |
| CNP520 2 mg | Summary of Plasma PK Parameter: T1/2 | 155 hour | Standard Deviation 40.9 |
| CNP520 10 mg | Summary of Plasma PK Parameter: T1/2 | 155 hour | Standard Deviation 33.9 |
| CNP520 35 mg | Summary of Plasma PK Parameter: T1/2 | 160 hour | Standard Deviation 22 |
Secondary
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.
Time frame: Days 1 and 91
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: Tlag | Day 1 (n=25,25,26,24) | 0.5 hour |
| Placebo | Summary of Plasma PK Parameter: Tlag | Day 91 (n=23,22,24,20) | 0 hour |
| CNP520 2 mg | Summary of Plasma PK Parameter: Tlag | Day 91 (n=23,22,24,20) | 0 hour |
| CNP520 2 mg | Summary of Plasma PK Parameter: Tlag | Day 1 (n=25,25,26,24) | 0.5 hour |
| CNP520 10 mg | Summary of Plasma PK Parameter: Tlag | Day 1 (n=25,25,26,24) | 0.5 hour |
| CNP520 10 mg | Summary of Plasma PK Parameter: Tlag | Day 91 (n=23,22,24,20) | 0 hour |
| CNP520 35 mg | Summary of Plasma PK Parameter: Tlag | Day 1 (n=25,25,26,24) | 0 hour |
| CNP520 35 mg | Summary of Plasma PK Parameter: Tlag | Day 91 (n=23,22,24,20) | 0 hour |
Secondary
Summary of Plasma PK Parameter: Tmax
Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax.
Time frame: Days 1 and 91
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Summary of Plasma PK Parameter: Tmax | Day 1 (n=25,25,26,24) | 2.5 hour |
| Placebo | Summary of Plasma PK Parameter: Tmax | Day 91 (n=23,22,24,20) | 2.5 hour |
| CNP520 2 mg | Summary of Plasma PK Parameter: Tmax | Day 91 (n=23,22,24,20) | 2.5 hour |
| CNP520 2 mg | Summary of Plasma PK Parameter: Tmax | Day 1 (n=25,25,26,24) | 2.5 hour |
| CNP520 10 mg | Summary of Plasma PK Parameter: Tmax | Day 1 (n=25,25,26,24) | 2.5 hour |
| CNP520 10 mg | Summary of Plasma PK Parameter: Tmax | Day 91 (n=23,22,24,20) | 2.5 hour |
| CNP520 35 mg | Summary of Plasma PK Parameter: Tmax | Day 1 (n=25,25,26,24) | 2.5 hour |
| CNP520 35 mg | Summary of Plasma PK Parameter: Tmax | Day 91 (n=23,22,24,20) | 2.5 hour |