Study to Assess Safety, Tolerability and Phamacokinetics of KAE609 Administered Intravenously in Healthy Subjects
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT04321252
Collaborator
Wellcome Trust (Other)
57
1
7
3.6
15.6
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
57 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Other
Official Title:
A Randomized, Subject and Investigator-blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of KAE609 Administered Intravenously in Healthy Subjects
Actual Study Start Date
:
Jul 22, 2020
Actual Primary Completion Date
:
Nov 10, 2020
Actual Study Completion Date
:
Nov 10, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A1: 10.5 mg/placebo Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort A2: 30 mg/placebo Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort A3: 75 mg/placebo Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort A4: 120 mg/placebo Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort A5: 210 mg/placebo Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
| Experimental: Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel. |
Drug: KAE609
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)
Drug: Placebo
matching placeo for iv administration
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Antwerpen | Belgium | B-2060 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
- Wellcome Trust
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04321252
Other Study ID Numbers:
- CKAE609X2111
- 2019-000405-71
- 217692/Z/19/Z
First Posted:
Mar 25, 2020
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted in one center in Belgium. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 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 |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. | All placebo-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | 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. | 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. | All placebo-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) |
| Period Title: Overall Study | |||||||||
| STARTED | 6 | 6 | 6 | 6 | 6 | 9 | 6 | 6 | 6 |
| PK Analysis Set | 6 | 6 | 6 | 6 | 6 | 0 | 6 | 6 | 0 |
| COMPLETED | 6 | 6 | 6 | 6 | 6 | 8 | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 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 | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. | All placebo-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | 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. | 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. | All placebo-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 9 | 6 | 6 | 6 | 57 |
| Age (Count of Participants) | ||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
6
100%
|
6
100%
|
6
100%
|
57
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | ||||||||||
| Female |
1
16.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
2
22.2%
|
1
16.7%
|
2
33.3%
|
5
83.3%
|
16
28.1%
|
| Male |
5
83.3%
|
4
66.7%
|
5
83.3%
|
5
83.3%
|
5
83.3%
|
7
77.8%
|
5
83.3%
|
4
66.7%
|
1
16.7%
|
41
71.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
6
100%
|
6
100%
|
6
100%
|
57
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
9
100%
|
6
100%
|
6
100%
|
6
100%
|
57
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled KAE609 | 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 KAE609 | Part B (Multiple-ascending Dose (MAD): Pooled Placebo |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. | All KAE609-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | All placebo-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | 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. | 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. | All KAE609-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) | All placebo-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 30 | 9 | 6 | 6 | 12 | 6 |
| Adverse Events (AEs) |
0
0%
|
1
16.7%
|
1
16.7%
|
2
33.3%
|
6
100%
|
10
111.1%
|
5
83.3%
|
4
66.7%
|
6
100%
|
10
17.5%
|
4
NaN
|
| Serious Adverse Events (SAEs) |
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Title | Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
412
(101)
|
1510
(1000)
|
2910
(1340)
|
5930
(1190)
|
6590
(1290)
|
| Title | Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Median (Full Range) [Hour (hr)] |
0.167
|
0.0333
|
0.333
|
0.167
|
0.167
|
| Title | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [h*ng/mL] |
2690
(977)
|
9540
(1640)
|
25400
(1770)
|
53700
(20900)
|
60800
(11600)
|
| Title | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [h*ng/mL] |
2770
(990)
|
9750
(1730)
|
25600
(1730)
|
57400
(22100)
|
62000
(11500)
|
| Title | Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [h*ng/mL] |
1450
(330)
|
4540
(673)
|
13500
(2230)
|
23200
(7920)
|
26200
(3600)
|
| Title | Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Hour (hr)] |
27.7
(8.89)
|
30.5
(6.79)
|
21.9
(6.76)
|
38.9
(12.8)
|
29.4
(5.39)
|
| Title | Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Milliliter/hour (mL/h)] |
4330
(1890)
|
3150
(507)
|
2940
(192)
|
2430
(1120)
|
3500
(700)
|
| Title | Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) |
|---|---|---|---|---|---|
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 |
| Mean (Standard Deviation) [Milliliter (mL)] |
154000
(20400)
|
138000
(34000)
|
92900
(29600)
|
124000
(32700)
|
151000
(50400)
|
| Title | Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Day 1 |
3920
(999)
|
4530
(705)
|
| Day 5 |
4630
(2670)
|
5540
(2090)
|
| Title | Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Day 1 |
0.100
|
0.167
|
| Day 5 |
0.0333
|
0.167
|
| Title | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [h*ng/mL] |
58500
(23000)
|
121000
(56100)
|
| Title | Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Day 1 |
13200
(1770)
|
16500
(2290)
|
| Day 5 |
20000
(4890)
|
40600
(11400)
|
| Title | Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Day 1 |
25.0
(8.16)
|
18.1
(2.83)
|
| Day 5 |
35.5
(8.58)
|
31.9
(12.5)
|
| Title | Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [Milliliter/hour (mL/h)] |
3140
(717)
|
3160
(907)
|
| Title | Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis set. Only participants with an evaluable PK sample collected at each timepoint were included in the analysis. |
| Arm/Group Title | Part B (Multiple-ascending Dose (MAD): Cohort B1 (KAE609 60 mg) | Part B (Multiple-ascending Dose (MAD): Cohort B2 (KAE609 120 mg) |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [Milliliter (mL)] |
175000
(14700)
|
173000
(29700)
|
Adverse Events
| Time Frame | On-treatment Adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed for up to 4 months. | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Any sign or symptom that occurs during the treatment period plus 30 days post-treatment. | |||||||||||||||||||||
| Arm/Group Title | Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled KAE609 | 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 KAE609 | Part B (Multiple-ascending Dose (MAD): Pooled Placebo | |||||||||||
| Arm/Group Description | Cohort A1 (SAD): Single iv bolus dose of KAE609 10.5 mg administered at the clinical site by the study personnel. | Cohort A2 (SAD): Single iv bolus dose of KAE609 30 mg administered at the clinical site by the study personnel. | Cohort A3 (SAD): Single iv infusion dose of KAE609 75 mg administered at the clinical site by the study personnel. | Cohort A4 (SAD): Single iv infusion dose of KAE609 120 mg administered at the clinical site by the study personnel. | Cohort A5 (SAD): Single iv infusion dose of KAE609 210 mg administered at the clinical site by the study personnel. | All KAE609-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | All placebo-treated patients from Part A (Single-ascending dose (SAD) cohorts (cohort A1, cohort A2, cohort A3, cohort A4 and cohort A5) | 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. | 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. | All KAE609-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) | All placebo-treated patients from Part B (Multiple-ascending dose (MAD) cohorts (cohort B1 and cohort B2) | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled KAE609 | 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 KAE609 | Part B (Multiple-ascending Dose (MAD): Pooled Placebo | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled KAE609 | 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 KAE609 | Part B (Multiple-ascending Dose (MAD): Pooled Placebo | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Testicular embryonal carcinoma | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Testicular malignant teratoma | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Part A (Single-ascending Dose (SAD): Cohort A1 (KAE609 10.5 mg) | 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 A4 (KAE609 120 mg) | Part A (Single-ascending Dose (SAD): Cohort A5 (KAE609 210 mg) | Part A (Single-ascending Dose (SAD): Pooled KAE609 | 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 KAE609 | Part B (Multiple-ascending Dose (MAD): Pooled Placebo | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/6 (33.3%) | 6/6 (100%) | 10/30 (33.3%) | 5/9 (55.6%) | 4/6 (66.7%) | 6/6 (100%) | 10/12 (83.3%) | 4/6 (66.7%) | |||||||||||
| Eye disorders | ||||||||||||||||||||||
| Abnormal sensation in eye | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Abdominal discomfort | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 1/6 (16.7%) | |||||||||||
| Diarrhoea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/12 (16.7%) | 2/6 (33.3%) | |||||||||||
| Dyspepsia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Eructation | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Nausea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/30 (6.7%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Vomiting | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Catheter site oedema | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 1/9 (11.1%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Catheter site pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Fatigue | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/12 (16.7%) | 1/6 (16.7%) | |||||||||||
| Infusion site discomfort | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Oral herpes | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||
| Infusion related reaction | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||||||||||
| Investigations | ||||||||||||||||||||||
| Alanine aminotransferase increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Aspartate aminotransferase increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Blood lactate dehydrogenase increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| C-reactive protein increased | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Electrocardiogram T wave inversion | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Electrocardiogram abnormal | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Arthralgia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Myalgia | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Neck pain | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Nervous system disorders | ||||||||||||||||||||||
| Dizziness | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) | 2/30 (6.7%) | 0/9 (0%) | 3/6 (50%) | 4/6 (66.7%) | 7/12 (58.3%) | 1/6 (16.7%) | |||||||||||
| Headache | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | 4/30 (13.3%) | 3/9 (33.3%) | 2/6 (33.3%) | 3/6 (50%) | 5/12 (41.7%) | 1/6 (16.7%) | |||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||
| Dysmenorrhoea | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||||||||||
| Semen discolouration | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 3/6 (50%) | 4/30 (13.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Dry skin | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (0%) | |||||||||||
| Pruritus | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/30 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||||||||||
| Vascular disorders | ||||||||||||||||||||||
| Flushing | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/30 (3.3%) | 0/9 (0%) | 0/6 (0%) | 0/6 (0%) | 0/12 (0%) | 0/6 (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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04321252
Other Study ID Numbers:
- CKAE609X2111
- 2019-000405-71
- 217692/Z/19/Z
First Posted:
Mar 25, 2020
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021