Trial Outcomes & Findings for An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib) (NCT NCT00608907)
NCT ID: NCT00608907
Last Updated: 2012-01-30
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
61 participants
Primary outcome timeframe
Cycle 3 day 14 (72 hours post last dose)
Results posted on
2012-01-30
Participant Flow
Participant milestones
| Measure |
VELCADE
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
VELCADE + Rifampicin
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
13
|
18
|
|
Overall Study
COMPLETED
|
18
|
13
|
17
|
|
Overall Study
NOT COMPLETED
|
12
|
0
|
1
|
Reasons for withdrawal
| Measure |
VELCADE
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
VELCADE + Rifampicin
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
6
|
0
|
1
|
|
Overall Study
Death
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
0
|
|
Overall Study
Progressive Disease
|
1
|
0
|
0
|
Baseline Characteristics
An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)
Baseline characteristics by cohort
| Measure |
VELCADE
n=30 Participants
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
VELCADE + Rifampicin
n=13 Participants
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
n=18 Participants
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Age Continuous
|
64.7 years
STANDARD_DEVIATION 10.86 • n=5 Participants
|
60.2 years
STANDARD_DEVIATION 9.97 • n=7 Participants
|
62.3 years
STANDARD_DEVIATION 11.72 • n=5 Participants
|
63.0 years
STANDARD_DEVIATION 10.91 • n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Cycle 3 day 14 (72 hours post last dose)Population: Pharmacokinetic (PK) evaluable population, include all subjects completed 3 cycles of treatment and all PK assessments during the first 3 cycles of the study.
Outcome measures
| Measure |
VELCADE + Rifampicin
n=6 Participants
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
n=7 Participants
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
VELCADE
n=12 Participants
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours
|
123 ng*h/mL
Standard Deviation 34.2 • Interval 48.14 to 63.06
|
170 ng*h/mL
Standard Deviation 64.5 • Interval 82.28 to 105.21
|
215 ng*h/mL
Standard Deviation 58.4
|
Adverse Events
VELCADE
Serious events: 14 serious events
Other events: 28 other events
Deaths: 0 deaths
VELCADE + Rifampicin
Serious events: 5 serious events
Other events: 13 other events
Deaths: 0 deaths
VELCADE + Dexamethasone
Serious events: 7 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
VELCADE
n=30 participants at risk
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
VELCADE + Rifampicin
n=13 participants at risk
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
n=18 participants at risk
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Cardiac disorders
Cardiopulmonary Failure
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Cardiac disorders
Ventricular Tachycardia
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
2/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Gastrointestinal disorders
Diarrhoea
|
3.3%
1/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Gastrointestinal disorders
Stomatitis
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Gastrointestinal disorders
Upper Gastrointestinal Haemorrhage
|
0.00%
0/30
|
7.7%
1/13
|
0.00%
0/18
|
|
General disorders
Asthenia
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
General disorders
Catheter Site Haemorrhage
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
General disorders
Death
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
General disorders
Disease Progression
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
General disorders
Fatigue
|
0.00%
0/30
|
7.7%
1/13
|
0.00%
0/18
|
|
General disorders
Malaise
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
General disorders
Pyrexia
|
3.3%
1/30
|
7.7%
1/13
|
0.00%
0/18
|
|
General disorders
Thrombosis in Device
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Infections and infestations
Bronchitis
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Bronchopneumonia
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Cellulitis
|
0.00%
0/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Infections and infestations
Device Related Infection
|
0.00%
0/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Infections and infestations
Escherichia Bacteraemia
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Infections and infestations
Escherichia Urinary Tract Infection
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Gastroenteritis
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Infection
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Lobar Pneumonia
|
3.3%
1/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Meningitis Listeria
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Pneumonia
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Infections and infestations
Viral Infection
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Femoral Neck Fracture
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Injury, poisoning and procedural complications
Spinal Compression Fracture
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Injury, poisoning and procedural complications
Wrist Fracture
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
3.3%
1/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Tumour Lysis Syndrome
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid Cancer
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Nervous system disorders
Paralysis
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Nervous system disorders
Syncope
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Renal and urinary disorders
Renal Failure
|
0.00%
0/30
|
0.00%
0/13
|
16.7%
3/18
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.7%
2/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
3.3%
1/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Vascular disorders
Circulatory Collapse
|
0.00%
0/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Vascular disorders
Hypotension
|
0.00%
0/30
|
7.7%
1/13
|
5.6%
1/18
|
Other adverse events
| Measure |
VELCADE
n=30 participants at risk
Control arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle.
|
VELCADE + Rifampicin
n=13 participants at risk
Treatment Arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg oral tablet once daily days 4 to 10 in cycle 3.
|
VELCADE + Dexamethasone
n=18 participants at risk
Treatment arm, bortezomib 1.3 mg/m\^2 IV bolus on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg oral tablet once daily days 1 to 4, and 9 to 12 in cycle 3.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
23.3%
7/30
|
23.1%
3/13
|
33.3%
6/18
|
|
Blood and lymphatic system disorders
Neutropenia
|
23.3%
7/30
|
46.2%
6/13
|
55.6%
10/18
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
26.7%
8/30
|
38.5%
5/13
|
44.4%
8/18
|
|
Eye disorders
Blepharitis
|
3.3%
1/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Eye disorders
Conjunctivitis
|
13.3%
4/30
|
23.1%
3/13
|
5.6%
1/18
|
|
Eye disorders
Eye pain
|
10.0%
3/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Eye disorders
Visual Acuity Reduced
|
0.00%
0/30
|
0.00%
0/13
|
16.7%
3/18
|
|
Gastrointestinal disorders
Abdominal Distension
|
13.3%
4/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Gastrointestinal disorders
Dry mouth
|
13.3%
4/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
3/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Gastrointestinal disorders
Dysphagia
|
6.7%
2/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Gastrointestinal disorders
Epigastric discomfort
|
3.3%
1/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Gastrointestinal disorders
Gastritis
|
3.3%
1/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Gastrointestinal disorders
Vomiting
|
26.7%
8/30
|
46.2%
6/13
|
16.7%
3/18
|
|
General disorders
Chills
|
13.3%
4/30
|
15.4%
2/13
|
5.6%
1/18
|
|
General disorders
Oedema Peripheral
|
26.7%
8/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Hepatobiliary disorders
Hepatic Function Abnormal
|
3.3%
1/30
|
15.4%
2/13
|
16.7%
3/18
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.3%
1/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Infections and infestations
Herpes Zoster
|
13.3%
4/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Infections and infestations
Influenza
|
3.3%
1/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
3/30
|
15.4%
2/13
|
0.00%
0/18
|
|
Infections and infestations
Oral Herpes
|
3.3%
1/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Infections and infestations
Sinusitis
|
3.3%
1/30
|
15.4%
2/13
|
5.6%
1/18
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
23.3%
7/30
|
15.4%
2/13
|
38.9%
7/18
|
|
Injury, poisoning and procedural complications
Rib Fracture
|
6.7%
2/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Investigations
Weight Decreased
|
6.7%
2/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
13.3%
4/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Enzyme Abnormality
|
3.3%
1/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.7%
2/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
3.3%
1/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
10.0%
3/30
|
15.4%
2/13
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
3.3%
1/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/30
|
0.00%
0/13
|
27.8%
5/18
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
3/30
|
15.4%
2/13
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/30
|
7.7%
1/13
|
16.7%
3/18
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.0%
3/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.7%
2/30
|
0.00%
0/13
|
16.7%
3/18
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
2/30
|
15.4%
2/13
|
11.1%
2/18
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
6.7%
2/30
|
23.1%
3/13
|
16.7%
3/18
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
13.3%
4/30
|
23.1%
3/13
|
27.8%
5/18
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
10.0%
3/30
|
23.1%
3/13
|
22.2%
4/18
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
3/30
|
7.7%
1/13
|
16.7%
3/18
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
20.0%
6/30
|
38.5%
5/13
|
22.2%
4/18
|
|
Nervous system disorders
Dizziness
|
16.7%
5/30
|
38.5%
5/13
|
11.1%
2/18
|
|
Nervous system disorders
Dysgeusia
|
3.3%
1/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Nervous system disorders
Headache
|
36.7%
11/30
|
23.1%
3/13
|
22.2%
4/18
|
|
Nervous system disorders
Neuralgia
|
10.0%
3/30
|
23.1%
3/13
|
33.3%
6/18
|
|
Nervous system disorders
Neuropathy Peripheral
|
3.3%
1/30
|
0.00%
0/13
|
11.1%
2/18
|
|
Nervous system disorders
Paraesthesia
|
3.3%
1/30
|
15.4%
2/13
|
16.7%
3/18
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
23.3%
7/30
|
46.2%
6/13
|
55.6%
10/18
|
|
Psychiatric disorders
Dysthymic Disorder
|
10.0%
3/30
|
0.00%
0/13
|
0.00%
0/18
|
|
Psychiatric disorders
Insomnia
|
20.0%
6/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Psychiatric disorders
Nightmare
|
6.7%
2/30
|
0.00%
0/13
|
5.6%
1/18
|
|
Renal and urinary disorders
Renal Impairment
|
10.0%
3/30
|
15.4%
2/13
|
11.1%
2/18
|
|
Reproductive system and breast disorders
Testicular Pain
|
6.7%
2/30
|
7.7%
1/13
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
6/30
|
38.5%
5/13
|
5.6%
1/18
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
2/30
|
15.4%
2/13
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
3.3%
1/30
|
7.7%
1/13
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
5/30
|
15.4%
2/13
|
22.2%
4/18
|
|
Skin and subcutaneous tissue disorders
Rash Generalised
|
3.3%
1/30
|
7.7%
1/13
|
11.1%
2/18
|
|
Vascular disorders
Hypertension
|
3.3%
1/30
|
7.7%
1/13
|
16.7%
3/18
|
|
Eye disorders
Dry Eye
|
3.3%
1/30
|
7.7%
1/13
|
22.2%
4/18
|
|
Gastrointestinal disorders
Nausea
|
36.7%
11/30
|
53.8%
7/13
|
33.3%
6/18
|
Additional Information
Helgi van de Velde, MD, PhD
Johnson & Johnson Pharmaceutical Research & Development
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place