Trial Outcomes & Findings for Single-arm Study to Assess the Safety of Hydromorphone Hydrochloride by Intrathecal Administration (NCT NCT01709747)
NCT ID: NCT01709747
Last Updated: 2021-08-25
Results Overview
Subjects with Clinical Signs and Symptoms of Granuloma \[Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.\]
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
364 participants
Primary outcome timeframe
12 months
Results posted on
2021-08-25
Participant Flow
Protocol states, "Approximately 350 subjects to be enrolled....... Additional subjects may be enrolled as deemed necessary to reach the study completion requirements for subjects on long term intrathecal hydromorphone hydrochloride therapy."
Participant milestones
| Measure |
Hydromorphone Hydrochloride
Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Overall Study
STARTED
|
364
|
|
Overall Study
COMPLETED
|
287
|
|
Overall Study
NOT COMPLETED
|
77
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Intent-to-Treat Population with non-missing data
Baseline characteristics by cohort
| Measure |
Hydromorphone Hydrochloride
n=364 Participants
Hydromorphone hydrochloride 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Age, Continuous
|
56.3 years
STANDARD_DEVIATION 10.3 • n=364 Participants
|
|
Sex: Female, Male
Female
|
220 Participants
n=364 Participants
|
|
Sex: Female, Male
Male
|
144 Participants
n=364 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=364 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
356 Participants
n=364 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=364 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
4 participants
n=364 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
16 participants
n=364 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 participants
n=364 Participants
|
|
Race/Ethnicity, Customized
White
|
338 participants
n=364 Participants
|
|
Race/Ethnicity, Customized
Multi-racial (no primary race)
|
2 participants
n=364 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 participants
n=364 Participants
|
|
Region of Enrollment
United States
|
364 Participants
n=364 Participants
|
|
Brief Pain Inventory (BPI)
|
5.44 units on a scale
STANDARD_DEVIATION 1.92 • n=358 Participants • Intent-to-Treat Population with non-missing data
|
|
Patient Global Impression of Change (PGIC)
|
4.24 units on a scale
STANDARD_DEVIATION 2.02 • n=357 Participants • Intent-to-Treat (ITT) Population with non-missing values
|
|
Visual Analog Scale Pain Intensity (VASPI)
|
48.16 mm
STANDARD_DEVIATION 26.69 • n=363 Participants • Intent-to-Treat (ITT) Population with non-missing assessment
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: All Enrolled Subjects
Subjects with Clinical Signs and Symptoms of Granuloma \[Note: The primary endpoint of this trial is Safety. There is no formal efficacy assessment planned in this open-label safety study.\]
Outcome measures
| Measure |
Hydromorphone Hydrochloride
n=364 Participants
Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Granulomas
Subjects with Clinical Signs and Symptoms of Granuloma
|
12 Participants
|
|
Granulomas
Subjects without Clinical Signs and Symptoms of Granuloma
|
352 Participants
|
|
Granulomas
MRI Confirms Granuloma
|
0 Participants
|
|
Granulomas
Investigator Considers Signs and Symptoms to be Caused by Granuloma
|
0 Participants
|
SECONDARY outcome
Timeframe: Early Termination/Final Visit through 12 monthsPopulation: ITT (Intent to Treat) with non-missing Baseline and Early Termination/Final Visit assessment for computing change from baseline
Change from Baseline in the Brief Pain Inventory (BPI). Pain Severity Measures, Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome. Therefore, a negative change from baseline indicates a better outcome. Outcome is Mean Pain Severity score calculated as the arithmetic mean of the Worst, Least, Average and Now scores. A negative change indicates better outcome.
Outcome measures
| Measure |
Hydromorphone Hydrochloride
n=334 Participants
Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Brief Pain Inventory (BPI) - Mean Pain Severity
|
-.20 units on a scale
Standard Deviation 1.80
|
SECONDARY outcome
Timeframe: Early Termination/Final Visit through 12 monthsPopulation: ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline
Change from Baseline in the Patient Global Impression of Change (PGIC). Scale: 7-point Likert scale, from 1 = No Change through 7 = A great deal better; a high score indicates a better outcome. Therefore, a positive change from baseline indicates a better outcome.
Outcome measures
| Measure |
Hydromorphone Hydrochloride
n=337 Participants
Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Patient Global Impression of Change (PGIC)
|
0.44 units on a scale
Standard Deviation 2.13
|
SECONDARY outcome
Timeframe: Early Termination/Final Visit through 12 monthsPopulation: ITT (Intent to Treat) with non-missing Baseline and Final Visit assessment for computing change from baseline
Change from Baseline in Visual Analog Scale Pain Intensity (VASPI). Scale: 0 mm = No Pain, 100 mm = Unbearable Pain; high score is worse. Therefore, a negative change from baseline indicates a better outcome.
Outcome measures
| Measure |
Hydromorphone Hydrochloride
n=344 Participants
Hydromorphone hydrochloride concentrations of 2 mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Visual Analog Scale Pain Intensity (VASPI)
|
-0.41 mm
Standard Deviation 26.10
|
Adverse Events
Hydromorphone Hydrochloride
Serious events: 71 serious events
Other events: 308 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Hydromorphone Hydrochloride
n=364 participants at risk
Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Infections and infestations
Cellulitis
|
1.9%
7/364 • 12 months
|
|
Infections and infestations
Pneumonia
|
1.6%
6/364 • 12 months
|
|
Infections and infestations
Sepsis
|
1.6%
6/364 • 12 months
|
|
Infections and infestations
Pyelonephritis Acute
|
0.55%
2/364 • 12 months
|
|
Infections and infestations
Bronchitis Viral
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Gastroenteritis Viral
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Implant Site Abscess
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Implant Site Infection
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Localised Infection
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Necrotising Fasciitis
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Osteomyelitis
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Pneumonia Bacterial
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Pyelonephritis
|
0.27%
1/364 • 12 months
|
|
Infections and infestations
Urinary Tract Infection
|
0.27%
1/364 • 12 months
|
|
Cardiac disorders
Cardiac Failure Congestive
|
0.82%
3/364 • 12 months
|
|
Cardiac disorders
Atrial Fibrillation
|
0.55%
2/364 • 12 months
|
|
Cardiac disorders
Angina Unstable
|
0.27%
1/364 • 12 months
|
|
Cardiac disorders
Atrial Flutter
|
0.27%
1/364 • 12 months
|
|
Cardiac disorders
Coronary Artery Disease
|
0.27%
1/364 • 12 months
|
|
Cardiac disorders
Myocardial Infarction
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Cerebrospinal Fistula
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Cognitive Disorder
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Encephalopathy
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Hepatic Encephalopathy
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Radiculopathy
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Somnolence
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Syncope
|
0.27%
1/364 • 12 months
|
|
Nervous system disorders
Uraemic Encephalopathy
|
0.27%
1/364 • 12 months
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.55%
2/364 • 12 months
|
|
Gastrointestinal disorders
Vomiting
|
0.55%
2/364 • 12 months
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.27%
1/364 • 12 months
|
|
Gastrointestinal disorders
Colitis
|
0.27%
1/364 • 12 months
|
|
Gastrointestinal disorders
Colitis Ischaemic
|
0.27%
1/364 • 12 months
|
|
Gastrointestinal disorders
Pancreatitis Acute
|
0.27%
1/364 • 12 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.55%
2/364 • 12 months
|
|
Injury, poisoning and procedural complications
Subdural Haematoma
|
0.55%
2/364 • 12 months
|
|
Injury, poisoning and procedural complications
Accidental Overdose
|
0.27%
1/364 • 12 months
|
|
Injury, poisoning and procedural complications
Contusion
|
0.27%
1/364 • 12 months
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
0.27%
1/364 • 12 months
|
|
Injury, poisoning and procedural complications
Lower Limb Fracture
|
0.27%
1/364 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
|
1.1%
4/364 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.27%
1/364 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.27%
1/364 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.27%
1/364 • 12 months
|
|
General disorders
Chest Pain
|
0.55%
2/364 • 12 months
|
|
General disorders
Non-Cardiac Chest Pain
|
0.55%
2/364 • 12 months
|
|
General disorders
Chronic Fatigue Syndrome
|
0.27%
1/364 • 12 months
|
|
General disorders
Drug Withdrawal Syndrome
|
0.27%
1/364 • 12 months
|
|
General disorders
Systemic Inflammatory Response Syndrome
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.27%
1/364 • 12 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.27%
1/364 • 12 months
|
|
Psychiatric disorders
Mental Status Changes
|
0.82%
3/364 • 12 months
|
|
Psychiatric disorders
Bipolar Disorder
|
0.27%
1/364 • 12 months
|
|
Psychiatric disorders
Panic Attack
|
0.27%
1/364 • 12 months
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.82%
3/364 • 12 months
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.55%
2/364 • 12 months
|
|
Renal and urinary disorders
Cystitis Haemorrhagic
|
0.27%
1/364 • 12 months
|
|
Renal and urinary disorders
Obstructive Uropathy
|
0.27%
1/364 • 12 months
|
|
Renal and urinary disorders
Renal Colic
|
0.27%
1/364 • 12 months
|
|
Vascular disorders
Accelerated Hypertension
|
0.27%
1/364 • 12 months
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.27%
1/364 • 12 months
|
|
Vascular disorders
Haemorrhage
|
0.27%
1/364 • 12 months
|
|
Vascular disorders
Hypertension
|
0.27%
1/364 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.82%
3/364 • 12 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.27%
1/364 • 12 months
|
|
Congenital, familial and genetic disorders
Melas Syndrome
|
0.27%
1/364 • 12 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Carcinoma
|
0.27%
1/364 • 12 months
|
|
Skin and subcutaneous tissue disorders
Precancerous Skin Lesion
|
0.27%
1/364 • 12 months
|
Other adverse events
| Measure |
Hydromorphone Hydrochloride
n=364 participants at risk
Hydromorphone hydrochloride concentrations of 2mg/mL and 10 mg/mL for 0.1 mg/day to 10 mg/day based in dose titration, by intrathecal administration, 12 months safety evaluation
Hydromorphone Hydrochloride: Opioid for chronic pain
Programmable Implantable pump: Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
17.0%
62/364 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
9.6%
35/364 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.9%
25/364 • 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
6.9%
25/364 • 12 months
|
|
Infections and infestations
Urinary Tract Infection
|
6.9%
25/364 • 12 months
|
|
General disorders
Oedema Peripheral
|
5.2%
19/364 • 12 months
|
|
General disorders
Pain
|
5.2%
19/364 • 12 months
|
|
Nervous system disorders
Headache
|
5.5%
20/364 • 12 months
|
|
Gastrointestinal disorders
Nausea
|
14.0%
51/364 • 12 months
|
|
Gastrointestinal disorders
Vomiting
|
8.8%
32/364 • 12 months
|
Additional Information
Heather Kapushoc, Sr. Biostatistician
CTI Clinical Trial and Consulting Services
Phone: 571-315-2574
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place