Malaria
Conditions
Keywords
safety, tolerability, pharmacokinetics, healthy volunteers, phase 1, malaria, intravenous, iv, KAE609, Placebo
Brief summary
This was a randomized, subject and investigator-blinded, placebo-controlled, single and multiple ascending intravenous (iv) dose study in healthy subjects to assess the safety and tolerability of KAE609 given in the vein.
Detailed description
The study consisted of 2 parts: single-ascending dose (SAD) part and multiple ascending dose (MAD) part. In Part A (Single-ascending dose (SAD) part), it was planned to recruit 6 active, 2 placebo subjects in each cohort: * Cohort A1: 10.5 mg/placebo * Cohort A2: 30 mg/placebo * Cohort A3: 75 mg/placebo * Cohort A4: 120 mg/placebo * Cohort A5: 210 mg/placebo In Part B (Multiple-ascending dose (MAD) part), Subjects were assigned to one of the following treatment arms in a ratio of 2:1 (6 active, 3 placebo): * Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days * Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days Eligible subjects were randomized to receive a single or q24h x 5 doses of either KAE609 or placebo. Safety, tolerability and pharmacokinetics were assessed over the period of 8 days for single dose and 12 days for multiple dose up to end of study visit for each subject.
Interventions
DRUGKAE609
* iv bolus administration over approximately 2 min for doses \< 75 mg (Cohorts A1, A2 and B1) * iv infusion over approximately 10 min for doses ≥ 75 mg (Cohorts A3, A4, A5 and B2)
DRUGPlacebo
matching placeo for iv administration
Sponsors
Wellcome Trust
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy male and female subjects 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests. * Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 30.0 kg/m2. Key
Exclusion criteria
* Use of other investigational drugs within 5 half-lives of Screening, or within 30 days of dosing, whichever is longer; or longer if required by local regulations. * Significant illness which has not resolved within two (2) weeks prior to initial dosing. * Pregnant or nursing (lactating) women. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. * Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for at least 2 weeks after last dose of investigational drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | From study treatment start date till 30 days safety follow-up, assessed for up to 4 months | The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUCinf was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
| Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr) | Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. |
Countries
Belgium
Participant flow
Recruitment details
This study was conducted in one center in Belgium.
Participants by arm
| Arm | Count |
|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | 6 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | 6 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | 6 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | 6 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. | 6 |
| Part A (Single-ascending Dose (SAD): Pooled Placebo All placebo-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | 9 |
| Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) Cohort B1 (MAD): Multiple iv bolus doses of KAE609 (60 mg, every 24 hours (q24h) × 5 days) administered at the clinical site by the study personnel. | 6 |
| Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) Cohort B2 (MAD): Multiple iv infusion doses of KAE609 (120 mg, every 24 hours (q24h) × 5 days) administered at the clinical site by the study personnel. | 6 |
| Part B (Multiple-ascending Dose (MAD): Pooled Placebo All placebo-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) | 6 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled Placebo | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) | Part B (Multiple-ascending Dose (MAD): Pooled Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 57 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 16 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 41 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 7 Participants | 5 Participants | 4 Participants | 1 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 30 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 6 / 6 | 10 / 30 | 5 / 9 | 4 / 6 | 6 / 6 | 10 / 12 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 1 / 30 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 |
Outcome results
Primary
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths
The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: From study treatment start date till 30 days safety follow-up, assessed for up to 4 months
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 1 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 1 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 1 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 2 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 6 Participants |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 1 Participants |
| Part A (Single-ascending Dose (SAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 10 Participants |
| Part A (Single-ascending Dose (SAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part A (Single-ascending Dose (SAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 5 Participants |
| Part A (Single-ascending Dose (SAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part A (Single-ascending Dose (SAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 4 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 6 Participants |
| Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 10 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled KAE609 | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Deaths | 0 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Adverse Events (AEs) | 4 Participants |
| Part B (Multiple-ascending Dose (MAD): Pooled Placebo | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths | Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 154000 Milliliter (mL) | Standard Deviation 20400 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 138000 Milliliter (mL) | Standard Deviation 34000 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 92900 Milliliter (mL) | Standard Deviation 29600 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 124000 Milliliter (mL) | Standard Deviation 32700 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 151000 Milliliter (mL) | Standard Deviation 50400 |
Secondary
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | 1450 h*ng/mL | Standard Deviation 330 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | 4540 h*ng/mL | Standard Deviation 673 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | 13500 h*ng/mL | Standard Deviation 2230 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | 23200 h*ng/mL | Standard Deviation 7920 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | 26200 h*ng/mL | Standard Deviation 3600 |
Secondary
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUCinf was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | 2770 h*ng/mL | Standard Deviation 990 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | 9750 h*ng/mL | Standard Deviation 1730 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | 25600 h*ng/mL | Standard Deviation 1730 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | 57400 h*ng/mL | Standard Deviation 22100 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | 62000 h*ng/mL | Standard Deviation 11500 |
Secondary
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 2690 h*ng/mL | Standard Deviation 977 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 9540 h*ng/mL | Standard Deviation 1640 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 25400 h*ng/mL | Standard Deviation 1770 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 53700 h*ng/mL | Standard Deviation 20900 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 60800 h*ng/mL | Standard Deviation 11600 |
Secondary
Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 4330 Milliliter/hour (mL/h) | Standard Deviation 1890 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 3150 Milliliter/hour (mL/h) | Standard Deviation 507 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 2940 Milliliter/hour (mL/h) | Standard Deviation 192 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 2430 Milliliter/hour (mL/h) | Standard Deviation 1120 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 3500 Milliliter/hour (mL/h) | Standard Deviation 700 |
Secondary
Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | 412 ng/mL | Standard Deviation 101 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | 1510 ng/mL | Standard Deviation 1000 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | 2910 ng/mL | Standard Deviation 1340 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | 5930 ng/mL | Standard Deviation 1190 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | 6590 ng/mL | Standard Deviation 1290 |
Secondary
Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | 27.7 Hour (hr) | Standard Deviation 8.89 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | 30.5 Hour (hr) | Standard Deviation 6.79 |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | 21.9 Hour (hr) | Standard Deviation 6.76 |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | 38.9 Hour (hr) | Standard Deviation 12.8 |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | 29.4 Hour (hr) | Standard Deviation 5.39 |
Secondary
Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics.
Time frame: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.167 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.0333 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A3 (KAE609 75 mg) | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.333 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A4 (KAE609 120 mg) | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.167 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.167 Hour (hr) |
Secondary
Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 175000 Milliliter (mL) | Standard Deviation 14700 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) | 173000 Milliliter (mL) | Standard Deviation 29700 |
Secondary
Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Day 1 | 13200 h*ng/mL | Standard Deviation 1770 |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Day 5 | 20000 h*ng/mL | Standard Deviation 4890 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Day 1 | 16500 h*ng/mL | Standard Deviation 2290 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) | Day 5 | 40600 h*ng/mL | Standard Deviation 11400 |
Secondary
Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 58500 h*ng/mL | Standard Deviation 23000 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) | 121000 h*ng/mL | Standard Deviation 56100 |
Secondary
Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 3140 Milliliter/hour (mL/h) | Standard Deviation 717 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration | 3160 Milliliter/hour (mL/h) | Standard Deviation 907 |
Secondary
Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Day 1 | 3920 ng/mL | Standard Deviation 999 |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Day 5 | 4630 ng/mL | Standard Deviation 2670 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Day 1 | 4530 ng/mL | Standard Deviation 705 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) | Day 5 | 5540 ng/mL | Standard Deviation 2090 |
Secondary
Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.
Time frame: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Day 1 | 25.0 Hour (hr) | Standard Deviation 8.16 |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Day 5 | 35.5 Hour (hr) | Standard Deviation 8.58 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Day 1 | 18.1 Hour (hr) | Standard Deviation 2.83 |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) | Day 5 | 31.9 Hour (hr) | Standard Deviation 12.5 |
Secondary
Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics.
Time frame: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Population: PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 1 | 0.100 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 5 | 0.0333 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 1 | 0.167 Hour (hr) |
| Part A (Single-ascending Dose (SAD): Cohort A2 (KAE609 30 mg) | Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 5 | 0.167 Hour (hr) |