Sporadic Inclusion Body Myositis (sIBM)
Conditions
Keywords
Inclusion Body Myositis (IBM)
Brief summary
This study is an open-label, long-term study for those patients who participated in the prior proof-of-concept protocol, in which the preliminary efficacy for BYM338 in patients with sIBM was demonstrated after a single 30 mg/kg i.v. dose of BYM338. This study is designed to confirm the efficacy, safety and tolerability of BYM338 in sIBM with long-term dosing. However due to lack of efficacy in patients with sIBM, the study was terminated early.
Detailed description
This is a non-confirmatory, multicenter, open-label, non-randomized trial which will extend active treatment to those patients that participated in the preceding proof-of-concept study (CBYM338X2205) in order to collect long-term safety and tolerability data. Up to 14 patients with sIBM will be invited to enroll into the study to receive BYM338 open-label for a period of approximately 3 years or until BYM338 is commercially available, whichever comes first. The study consists of a maximum 28-day screening period, a 5-day baseline period, and a treatment period consisting of the site visits at 4-week intervals for treatment administration, safety and pharmacokinetic follow-up. All patients will be administered a medium level i.v. BYM338 dose regardless of their treatment allocation in the prior study.
Interventions
DRUGBYM338 (Bimagrumab)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent must be obtained before any assessment is performed. * Patients who participated in the CBYM338X2205 study. A patient is defined as participating in the study if they were enrolled and received study medication. * Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Exclusion criteria
* Patients for whom the treating physician considers it inappropriate for continuation into the study, including consideration of physical and laboratory assessment of the patient at screening. * Patients who were non-compliant or demonstrated a serious protocol deviation in the previous study. * Use of other investigational drugs at the time of enrollment, within 30 days or 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations. * History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes * Swallowing difficulty or other reason that precludes adequate intake of energy and protein, defined as at least 20 kcal/kg/day and 0.6 g protein/kg/day as determined by the investigators assessment. * On the Columbia-Suicide Severity Rating Scale, a score of 4 or 5 on the Suicidal Ideation item or any yes on the Suicidal Behavior item that is related to suicidal behavior occurring during the last 2 years. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and for 5 half-lives (14 weeks) after stopping treatment. Highly effective contraception is defined as either: 1. Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]. 2. Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 3. Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). \[For female study subjects, the vasectomized male partner should be the sole partner for that patient\]. 4. Use of a combination of any two of the following (a+b or a+c or b+c): <!-- --> 1. Use of oral, injected or implanted hormonal methods of contraception. 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of \> 40 IU/L (or as determined by the cut off used by the local clinical laboratory) at screening. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the eCRF. All female patients must have negative pregnancy test results at screening and baseline. * Use of oral beta agonists, oral corticosteroids, androgens or androgen inhibitors (including LHRH agonists), or intravenous gamma globulin (IVIG) within the previous 6 months. Short-term corticosteroids for unrelated indications, defined as \< 20 mg/d for \< 30 days and ending at least 60 days prior to screening, are acceptable. * Patients with known bleeding disorders, or who are under treatment with anti-coagulants. * A presence or history of clinically relevant ECG abnormalities, or including but not limited to Long QT syndrome, ischemic changes that cannot be shown to be stable for at least 6 months by previous ECG, or 2nd degree Mobitz II or 3rd degree heart block. * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. * Significant illness which has not resolved within two (2) weeks prior to initial dosing. * A positive HIV, Hepatitis B surface antigen or Hepatitis C test result. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Up to 29 month | Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 29, 85, 169, 253, 337, 421, 505, 589, 673, 757, 1177 | To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1. Pre-dose only on each subsequent administration |
| Changes From Baseline in Physical Function Reported by Patients | Baseline, Week 104 | Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. Due to the no-signal this analysis was cancelled. |
| Changes From Baseline in Muscle Strength. | Baseline, Day 1, 113, 169, 365, 533, 729 | Quadriceps muscle strength was measured, Quadriceps Quantitative Muscle Testing (QMT) by portable fixed dynamometry (PFD). A negative change from baseline indicates deterioration |
| Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Baseline,Day 1, 113, 169, 365, 533, 729 | The effect of BYM338 on additional muscle function measures (hand-grip and pinch-grip dynamometry). |
| Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Baseline, Day 1, 57, 113, 169, 365, 533, and day 729 | To assess the effect of multiple doses of BYM338 on lean body mass as measured by DXA in terms of change from baseline. |
| Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan | Baseline, Day 1, 57, 113 | Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was equal or more than 2% at Week 8 and 16 were considered responders |
| Pharmacokinetics (PK) Parameter of Cmax | Day 1 | To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1. |
| Time to Reach the Maximum Concentration After Drug Administration (Tmax) | Day 1 | The time to reach the maximum concentration after drug administration |
| Changes From Baseline in Muscle Function 6 Minute Walking Distance | Baseline,Day 1, 113, 169, 365, 533, 729 | The effect of BYM338 on additional muscle function measures (6 minute walking distance). The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement. |
Countries
United States
Participant flow
Recruitment details
Due to lack of efficacy in patients with sIBM, the study was terminated early.
Participants by arm
| Arm | Count |
|---|---|
| BYM338 BYM338 Group | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 7 |
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | BYM338 |
|---|---|
| Age, Continuous | 70.1 Years STANDARD_DEVIATION 10.39 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity
Time frame: Up to 29 month
Population: safety analysis set - included all patients that received at least one dose of study drug. No statistical analysis provided for Number of Participants Who Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) During this extension study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BYM338 | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Death | 0 Participants |
| BYM338 | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Serious adverse events (SAE) | 2 Participants |
| BYM338 | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse Events (AE) | 10 Participants |
Secondary
Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan
Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was equal or more than 2% at Week 8 and 16 were considered responders
Time frame: Baseline, Day 1, 57, 113
Population: Pharmacodynamics (PD) analysis set: Patients with available PD data and no protocol deviations with relevant impact on PD data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan | Day 1 | 0 Percentage Change | Standard Deviation 0 |
| BYM338 | Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan | Day 57 | 4.14 Percentage Change | Standard Deviation 4.25 |
| BYM338 | Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan | Day 113 | 4.51 Percentage Change | Standard Deviation 6.3 |
Secondary
Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA)
To assess the effect of multiple doses of BYM338 on lean body mass as measured by DXA in terms of change from baseline.
Time frame: Baseline, Day 1, 57, 113, 169, 365, 533, and day 729
Population: Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 1 | 0 Percentage Change in LBM | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 57 | 4.292 Percentage Change in LBM | Standard Deviation 2.748 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 113 | 5.552 Percentage Change in LBM | Standard Deviation 3.6066 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 365 | 6.919 Percentage Change in LBM | Standard Deviation 2.9669 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 533 | 6.885 Percentage Change in LBM | Standard Deviation 3.7894 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 169 | 7.463 Percentage Change in LBM | Standard Deviation 4.5687 |
| BYM338 | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | Day 729 | 0.727 Percentage Change in LBM | — |
Secondary
Changes From Baseline in Muscle Function 6 Minute Walking Distance
The effect of BYM338 on additional muscle function measures (6 minute walking distance). The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement.
Time frame: Baseline,Day 1, 113, 169, 365, 533, 729
Population: Pharmacodynamics (PD) analysis set: Patients with available PD data and no protocol deviations with relevant impact on PD data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 1 | 0 Meters | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 113 | -1.56 Meters | Standard Deviation 13.685 |
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 169 | -7.41 Meters | Standard Deviation 12.463 |
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 365 | -8.97 Meters | Standard Deviation 15.763 |
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 533 | -16.99 Meters | Standard Deviation 22.382 |
| BYM338 | Changes From Baseline in Muscle Function 6 Minute Walking Distance | Day 729 | -17.86 Meters | — |
Secondary
Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry)
The effect of BYM338 on additional muscle function measures (hand-grip and pinch-grip dynamometry).
Time frame: Baseline,Day 1, 113, 169, 365, 533, 729
Population: Pharmacodynamics (PD) analysis set: Patients with available PD data and no protocol deviations with relevant impact on PD data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 729 | -8.41 Newtons | Standard Deviation 46.672 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 113 | 25.58 Newtons | Standard Deviation 37.544 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 169 | 21.36 Newtons | Standard Deviation 43.815 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 365 | -1.42 Newtons | Standard Deviation 47.973 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 533 | 2.78 Newtons | Standard Deviation 16.934 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand-grip day 729 | 8.95 Newtons | Standard Deviation 24.034 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 113 | 99.59 Newtons | Standard Deviation 184.472 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 169 | 109.05 Newtons | Standard Deviation 214.248 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 365 | 77.46 Newtons | Standard Deviation 160.133 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 533 | 53.99 Newtons | Standard Deviation 127.776 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand-grip day 729 | 163.66 Newtons | Standard Deviation 237.402 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 113 | 7.82 Newtons | Standard Deviation 27.292 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 169 | -4.74 Newtons | Standard Deviation 20.21 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 365 | -7.30 Newtons | Standard Deviation 35.224 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Left hand pinch grip day 533 | -11.40 Newtons | Standard Deviation 21.204 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 113 | -7.55 Newtons | Standard Deviation 26.792 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 169 | -9.35 Newtons | Standard Deviation 30.942 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 365 | 0.59 Newtons | Standard Deviation 32.094 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 533 | -8.65 Newtons | Standard Deviation 21.491 |
| BYM338 | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | Right hand pinch grip day 729 | -35.40 Newtons | Standard Deviation 44.82 |
Secondary
Changes From Baseline in Muscle Strength.
Quadriceps muscle strength was measured, Quadriceps Quantitative Muscle Testing (QMT) by portable fixed dynamometry (PFD). A negative change from baseline indicates deterioration
Time frame: Baseline, Day 1, 113, 169, 365, 533, 729
Population: Pharmacodynamics (PD) analysis set: Patients with available PD data and no protocol deviations with relevant impact on PD data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Changes From Baseline in Muscle Strength. | Quadriceps score left side Day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Strength. | left side Day 113 | -5.80 Newtons | Standard Deviation 28.16 |
| BYM338 | Changes From Baseline in Muscle Strength. | left side Day 169 | -5.95 Newtons | Standard Deviation 26.587 |
| BYM338 | Changes From Baseline in Muscle Strength. | left side Day 365 | -9.51 Newtons | Standard Deviation 28.149 |
| BYM338 | Changes From Baseline in Muscle Strength. | left side Day 533 | -25.77 Newtons | Standard Deviation 21.321 |
| BYM338 | Changes From Baseline in Muscle Strength. | left side Day 729 | 178.26 Newtons | — |
| BYM338 | Changes From Baseline in Muscle Strength. | Quadriceps score Right side Day 1 | 0 Newtons | Standard Deviation 0 |
| BYM338 | Changes From Baseline in Muscle Strength. | Right side Day 113 | -4.83 Newtons | Standard Deviation 29.904 |
| BYM338 | Changes From Baseline in Muscle Strength. | Right side Day 169 | -22.81 Newtons | Standard Deviation 18.784 |
| BYM338 | Changes From Baseline in Muscle Strength. | Right side Day 365 | -11.63 Newtons | Standard Deviation 47.141 |
| BYM338 | Changes From Baseline in Muscle Strength. | Right side Day 533 | -31.00 Newtons | Standard Deviation 29.173 |
| BYM338 | Changes From Baseline in Muscle Strength. | Right side Day 729 | -57.66 Newtons | — |
Secondary
Changes From Baseline in Physical Function Reported by Patients
Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. Due to the no-signal this analysis was cancelled.
Time frame: Baseline, Week 104
Population: Due to the early study termination and the small sample size in this open-label trial, this PRO analysis was cancelled.
Secondary
Pharmacokinetics (PK) Parameter of Cmax
To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1.
Time frame: Day 1
Population: Pharmacokinetics (PK) Analysis set: Patients with available PK data and no protocol deviations with relevant impact on PK data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BYM338 | Pharmacokinetics (PK) Parameter of Cmax | 278 ug/mL | Standard Deviation 62.6 |
Secondary
Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing
To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1. Pre-dose only on each subsequent administration
Time frame: Day 29, 85, 169, 253, 337, 421, 505, 589, 673, 757, 1177
Population: Pharmacokinetics (PK) Analysis set: Patients with available PK data and no protocol deviations with relevant impact on PK data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 29 (n=10) | 13.4 ng/mL | Standard Deviation 5.01 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 85 (n=10) | 24.1 ng/mL | Standard Deviation 13.1 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 169 (n=10) | 26.3 ng/mL | Standard Deviation 15.9 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 253 (n=9) | 28.8 ng/mL | Standard Deviation 12.1 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 337 (n=10) | 24.4 ng/mL | Standard Deviation 14.6 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 421 (n=9) | 24.5 ng/mL | Standard Deviation 11.5 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 505 (n=8) | 28.3 ng/mL | Standard Deviation 10.6 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 589 (n=6) | 39.8 ng/mL | Standard Deviation 30.2 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 673 (n=2) | 20.5 ng/mL | Standard Deviation 1.98 |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 757 (n=1) | 20.3 ng/mL | — |
| BYM338 | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | Day 1177 (n=1) | 31.4 ng/mL | — |
Secondary
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
The time to reach the maximum concentration after drug administration
Time frame: Day 1
Population: Pharmacokinetics (PK) Analysis set: Patients with available PK data and no protocol deviations with relevant impact on PK data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BYM338 | Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 0.744 hr |