Trial Outcomes & Findings for BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia (NCT NCT01669174)
NCT ID: NCT01669174
Last Updated: 2016-05-03
Results Overview
Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
67 participants
Primary outcome timeframe
Baseline, Weeks 4, 8, 16, 24
Results posted on
2016-05-03
Participant Flow
Participant milestones
| Measure |
BYM338
30 mg/kg
|
Placebo
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Overall Study
STARTED
|
33
|
34
|
|
Overall Study
COMPLETED
|
27
|
28
|
|
Overall Study
NOT COMPLETED
|
6
|
6
|
Reasons for withdrawal
| Measure |
BYM338
30 mg/kg
|
Placebo
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Overall Study
Subject withdrew consent
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Administrative problems
|
1
|
2
|
Baseline Characteristics
BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia
Baseline characteristics by cohort
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
n=34 Participants
Placebo to BYM338 30mg/kg
|
Total
n=67 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.5 Years
STANDARD_DEVIATION 5.93 • n=5 Participants
|
63.1 Years
STANDARD_DEVIATION 7.51 • n=7 Participants
|
63.7 Years
STANDARD_DEVIATION 6.76 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 4, 8, 16, 24Population: Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.
Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders.
Outcome measures
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
n=34 Participants
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
Week 4 Day 29 (n=30,31)
|
5.87 Percentage Change of TMV
Standard Deviation 3.413
|
0.02 Percentage Change of TMV
Standard Deviation 3.261
|
|
Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
Week 8 Day 57 (n=27,27)
|
7.01 Percentage Change of TMV
Standard Deviation 3.707
|
-0.65 Percentage Change of TMV
Standard Deviation 2.752
|
|
Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
Week 16 Day 113 (27,28)
|
7.84 Percentage Change of TMV
Standard Deviation 5.052
|
-0.88 Percentage Change of TMV
Standard Deviation 4.471
|
|
Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24
End of Study, week 24 (n=27,28)
|
5.04 Percentage Change of TMV
Standard Deviation 4.872
|
-1.31 Percentage Change of TMV
Standard Deviation 4.282
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 16, 24Population: Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame
Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD)
Outcome measures
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
n=34 Participants
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Change in 6 Minute Walk Distance Compared to Placebo
End of Study week 24 (n=27, 28)
|
374.9 meter
Standard Deviation 98.29
|
378.8 meter
Standard Deviation 81.50
|
|
Change in 6 Minute Walk Distance Compared to Placebo
Week 4 Day 29 (n=30,32)
|
364.6 meter
Standard Deviation 85.45
|
388.5 meter
Standard Deviation 100.22
|
|
Change in 6 Minute Walk Distance Compared to Placebo
Week 8 Day 57 (n=27,29)
|
373.9 meter
Standard Deviation 101.42
|
387.4 meter
Standard Deviation 99.73
|
|
Change in 6 Minute Walk Distance Compared to Placebo
Week 12 Day 85 (n=27,28)
|
383.0 meter
Standard Deviation 84.63
|
385.6 meter
Standard Deviation 107.62
|
|
Change in 6 Minute Walk Distance Compared to Placebo
Week 16 Day 113 (n=25,28)
|
379.7 meter
Standard Deviation 83.78
|
352.9 meter
Standard Deviation 104.01
|
SECONDARY outcome
Timeframe: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dosePopulation: Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.
The observed maximum plasma concentration following drug administration
Outcome measures
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Maximum Observed Serum Concentration (Cmax)
Cmax dose 1 (n=31)
|
614 ug/mL
Standard Deviation 143
|
—
|
|
Maximum Observed Serum Concentration (Cmax)
Cmax dose 2 (n=26)
|
580 ug/mL
Standard Deviation 121
|
—
|
SECONDARY outcome
Timeframe: 24 weeksPopulation: Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.
The time to reach the maximum concentration after drug administration
Outcome measures
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Tmax dose 1 (n=31)
|
2.22 hr
Full Range NA • Interval 2.02 to 3.17
|
—
|
|
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Tmax dose 2 (n=26)
|
2.23 hr
Full Range NA • Interval 1.97 to 3.2
|
—
|
SECONDARY outcome
Timeframe: 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dosePopulation: Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.
AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only.
Outcome measures
| Measure |
BYM338
n=33 Participants
30 mg/kg
|
Placebo
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
AUC0-56 and AUClast
AUC0-56 dose 1 (n=26)
|
4540 day*ug/mL
Standard Deviation 897
|
—
|
|
AUC0-56 and AUClast
AUC0-56 dose 2 (n=25)
|
5790 day*ug/mL
Standard Deviation 1300
|
—
|
|
AUC0-56 and AUClast
AUClast dose 2 (n=25)
|
7480 day*ug/mL
Standard Deviation 2080
|
—
|
Adverse Events
BYM338 30mg/kg
Serious events: 4 serious events
Other events: 31 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BYM338 30mg/kg
n=33 participants at risk
BYM338 30mg/kg
|
Placebo
n=34 participants at risk
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Gastrointestinal disorders
Inguinal hernia
|
3.0%
1/33
|
0.00%
0/34
|
|
Infections and infestations
Pneumonia
|
6.1%
2/33
|
2.9%
1/34
|
|
Infections and infestations
Postoperative wound infection
|
3.0%
1/33
|
0.00%
0/34
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
3.0%
1/33
|
0.00%
0/34
|
|
Injury, poisoning and procedural complications
Hip fracture
|
3.0%
1/33
|
0.00%
0/34
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
3.0%
1/33
|
0.00%
0/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/33
|
2.9%
1/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Throat cancer
|
3.0%
1/33
|
0.00%
0/34
|
|
Nervous system disorders
Haemorrhage intracranial
|
3.0%
1/33
|
0.00%
0/34
|
|
Renal and urinary disorders
Haematuria
|
3.0%
1/33
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/33
|
2.9%
1/34
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/33
|
2.9%
1/34
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.0%
1/33
|
0.00%
0/34
|
Other adverse events
| Measure |
BYM338 30mg/kg
n=33 participants at risk
BYM338 30mg/kg
|
Placebo
n=34 participants at risk
Placebo to BYM338 30mg/kg
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/33
|
5.9%
2/34
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.1%
2/33
|
0.00%
0/34
|
|
Gastrointestinal disorders
Diarrhoea
|
21.2%
7/33
|
8.8%
3/34
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
2/33
|
0.00%
0/34
|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33
|
2.9%
1/34
|
|
General disorders
Fatigue
|
6.1%
2/33
|
8.8%
3/34
|
|
General disorders
Feeling abnormal
|
12.1%
4/33
|
8.8%
3/34
|
|
General disorders
Feeling cold
|
6.1%
2/33
|
0.00%
0/34
|
|
General disorders
Influenza like illness
|
6.1%
2/33
|
0.00%
0/34
|
|
General disorders
Oedema peripheral
|
0.00%
0/33
|
5.9%
2/34
|
|
General disorders
Pain
|
0.00%
0/33
|
5.9%
2/34
|
|
Infections and infestations
Gastroenteritis
|
6.1%
2/33
|
2.9%
1/34
|
|
Infections and infestations
Nasopharyngitis
|
12.1%
4/33
|
0.00%
0/34
|
|
Infections and infestations
Pneumonia
|
3.0%
1/33
|
5.9%
2/34
|
|
Infections and infestations
Rash pustular
|
9.1%
3/33
|
5.9%
2/34
|
|
Infections and infestations
Sinusitis
|
9.1%
3/33
|
0.00%
0/34
|
|
Infections and infestations
Upper respiratory tract infection
|
6.1%
2/33
|
11.8%
4/34
|
|
Injury, poisoning and procedural complications
Contusion
|
6.1%
2/33
|
5.9%
2/34
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/33
|
5.9%
2/34
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
3.0%
1/33
|
5.9%
2/34
|
|
Investigations
Alanine aminotransferase increased
|
9.1%
3/33
|
0.00%
0/34
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
3/33
|
0.00%
0/34
|
|
Investigations
Blood alkaline phosphatase increased
|
6.1%
2/33
|
0.00%
0/34
|
|
Investigations
Blood creatine phosphokinase increased
|
6.1%
2/33
|
5.9%
2/34
|
|
Investigations
Blood glucose increased
|
6.1%
2/33
|
2.9%
1/34
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.1%
3/33
|
0.00%
0/34
|
|
Investigations
Haemoglobin urine present
|
6.1%
2/33
|
5.9%
2/34
|
|
Investigations
Urine leukocyte esterase positive
|
6.1%
2/33
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.1%
2/33
|
2.9%
1/34
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.1%
4/33
|
11.8%
4/34
|
|
Musculoskeletal and connective tissue disorders
Joint lock
|
6.1%
2/33
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
78.8%
26/33
|
47.1%
16/34
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
54.5%
18/33
|
14.7%
5/34
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
45.5%
15/33
|
26.5%
9/34
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
9.1%
3/33
|
2.9%
1/34
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
9.1%
3/33
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
21.2%
7/33
|
17.6%
6/34
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/33
|
5.9%
2/34
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
24.2%
8/33
|
20.6%
7/34
|
|
Nervous system disorders
Dizziness
|
9.1%
3/33
|
8.8%
3/34
|
|
Nervous system disorders
Headache
|
9.1%
3/33
|
23.5%
8/34
|
|
Nervous system disorders
Paraesthesia
|
9.1%
3/33
|
2.9%
1/34
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/33
|
5.9%
2/34
|
|
Psychiatric disorders
Depression
|
3.0%
1/33
|
8.8%
3/34
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
48.5%
16/33
|
35.3%
12/34
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.1%
4/33
|
14.7%
5/34
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
15.2%
5/33
|
14.7%
5/34
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/33
|
5.9%
2/34
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.1%
2/33
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.1%
3/33
|
2.9%
1/34
|
|
Skin and subcutaneous tissue disorders
Blister
|
6.1%
2/33
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/33
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
6.1%
2/33
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
Erythema
|
12.1%
4/33
|
11.8%
4/34
|
|
Skin and subcutaneous tissue disorders
Papule
|
6.1%
2/33
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/33
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.2%
5/33
|
20.6%
7/34
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/33
|
5.9%
2/34
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/33
|
8.8%
3/34
|
|
Vascular disorders
Haematoma
|
6.1%
2/33
|
2.9%
1/34
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
- Publication restrictions are in place
Restriction type: OTHER