Interstitial Cystitis
Conditions
Keywords
Interstitial cystitis, Humira, Adalimumab
Brief summary
The purpose of this study is to evaluate an investigational treatment for interstitial cystitis. Interstitial cystitis is a chronic bladder disease that includes the following symptoms: Urinary frequency during the day,urinary frequency at night, urinary urgency and bladder discomfort relieved by voiding. Presently, there is no cure for interstitial cystitis. The response to current treatments is poor. Patients with interstitial cystitis have a poorer quality of life. The cause of interstitial cystitis is unknown. This study is evaluating the drug Humira® (adalimumab) for improving the symptoms of patients with interstitial cystitis. Humira® is an injectable anti-inflammatory medication that has been available for use since December 31, 2002. Humira® has been FDA approved for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, and Crohn's disease. These diseases have similar characteristics to interstitial cystitis. This study will evaluate an investigational use of Humira® for the treatment of interstitial cystitis.
Detailed description
Interstitial cystitis (IC) is a chronic disabling bladder syndrome characterized by urinary frequency, nocturia, urinary urgency, and pain with bladder filling-relieved by emptying. There is no cure for IC and the treatment options are suboptimal. Patients with IC report significant negative effects on their physical and mental quality of life. The etiology of IC is unknown. Certain aspects of IC suggest that autoimmunity may play a role in initiating or sustaining the chronic inflammatory response. Bladder biopsies of patients with IC demonstrate an increase number of mast cells. Mast cell activation with the release of tumor necrosis factor (TNF) may mediate this bladder inflammation. Humira® (adalimumab) is a medication that blocks the effect of TNF. Humira® (adalimumab) is FDA approved for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, and Crohn's disease. These diseases are similar to IC. In this study, the hypothesis being tested is that Humira® (adalimumab) will show efficacy at reducing the symptoms of IC.
Interventions
DRUGAdalimumab
80 mg loading dose given subcutaneously followed by 40 mg dose given subcutaneously every two weeks over a twelve week period
OTHERinactive drug
80 mg loading dose given subcutaneously followed by 40 mg dose given subcutaneously every two weeks over a twelve week period
Sponsors
Abbott
ICStudy, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males or females ≥18 and ≤ 65 years of age previously diagnosed with Interstitial Cystitis * Currently have symptoms of urinary urgency, frequency or pain for more than 6 months * Urinating at least 7 times a day or having some urgency or pain (measured on linear analog scales) * Must be post-menopausal or surgically sterile or willing to use an adequate form of birth control * Not pregnant or lactating * Capable of voiding independently * Willing to provide informed consent to participate
Exclusion criteria
* Have symptoms that are presently relieved on other medications for interstitial cystitis * Have absence of nocturia * Have symptoms that are relieved by antimicrobials or antibiotics. * Have a body mass index (BMI) of \>39 kg/m2 * Have uncontrolled hypertension * Have Type I or type 2 diabetes * Have active Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) infection, or who are known carriers (Hepatitis B) at Screening * Have a positive tuberculosis test at screening * Have had a urinary tract infection for 6 weeks * Have had bacterial cystitis in previous 3 months * Have had previous exposure to Humira® (adalimumab) * Have taken investigational medication within 30 days of screening * Have any other condition/disease which, in the opinion of the investigator, could compromise subject safety or confound the interpretation of study results * Are unable or unwilling to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score | Baseline/12 Weeks | Improvement in the O'Leary Sant Symptom and Problem Index from baseline to week 12 Total scores on a scale range: 0-36 (0, meaning no symptoms to 36, meaning the most severe symptoms) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interstitial Cystitis Symptom Index (ICSI) | Baseline/ 12 weeks | Improvement in O'Leary Sant Interstitial Cystitis Symptom Index (ICSI) Total scores on a range scale: 0-20 (0, meaning no symptoms, to 20, meaning the most severe symptoms) |
| Interstitial Cystitis Problem Index (ICPI) | Baseline/12 Weeks | Improvement in O'Leary Sant Interstitial Cystitis Problem Index (ICPI) Total scores on a scale: 0-16 (0, meaning no symptoms, to 16, meaning the most severe symptoms) |
| Pelvic Pain Urgency/Frequency (PUF) Score | Baseline12 Weeks | Pelvic Pain, Urgency/Frequency Symptom Scale Total scores on a scale range: 0-35 (0, meaning no symptoms, to 35, meaning the most severe symptoms) |
| Global Response Assessment (GRA) | Measured at12 Weeks | Percent(%) of patients who reported 50% or greater overall improvement in their condition. Score on a scale range (improvement 0%-100%) |
Countries
United States
Participant flow
Recruitment details
subject were recruited from medical practices and by advertisement starting March 2011 through January 2013.
Pre-assignment details
A total of 4 subjects did not meet screening criteria.
Participants by arm
| Arm | Count |
|---|---|
| Inactive Drug inactive drug : placebo | 22 |
| Adalimumab Adalimumab : 80 mg loading dose given subcutaneously followed by 40 mg dose given subcutaneously every two weeks over a twelve week period | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Adalimumab | Inactive Drug | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 22 Participants | 43 Participants |
| Age, Continuous | 45.2 years STANDARD_DEVIATION 14 | 46.5 years STANDARD_DEVIATION 13.4 | 45.9 years STANDARD_DEVIATION 13.7 |
| Region of Enrollment United States | 21 participants | 22 participants | 43 participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 22 | 17 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 |
Outcome results
Primary
O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score
Improvement in the O'Leary Sant Symptom and Problem Index from baseline to week 12 Total scores on a scale range: 0-36 (0, meaning no symptoms to 36, meaning the most severe symptoms)
Time frame: Baseline/12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Drug | O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score | Baseline | 27.7 units on a scale | Standard Deviation 4.9 |
| Inactive Drug | O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score | Week 12 | 19.6 units on a scale | Standard Deviation 10.7 |
| Adalimumab | O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score | Week 12 | 19.9 units on a scale | Standard Deviation 7.5 |
| Adalimumab | O'Leary-Santa Interstitial Cystitis Symptom Index and Problem Index (OSPI) Score | Baseline | 27.8 units on a scale | Standard Deviation 3.9 |
Comparison: Statistical improvement in the adalimumab group compared to the placebo group from baseline to week 12.p-value: 0.7595% CI: [4, 11.8]t-test, 2 sided
Secondary
Global Response Assessment (GRA)
Percent(%) of patients who reported 50% or greater overall improvement in their condition. Score on a scale range (improvement 0%-100%)
Time frame: Measured at12 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inactive Drug | Global Response Assessment (GRA) | 50 percentage of participants |
| Adalimumab | Global Response Assessment (GRA) | 53 percentage of participants |
Comparison: Statistical improvement in the adalimumab group compared to the placebo group from baseline to week 12.p-value: 0.67t-test, 2 sided
Secondary
Interstitial Cystitis Problem Index (ICPI)
Improvement in O'Leary Sant Interstitial Cystitis Problem Index (ICPI) Total scores on a scale: 0-16 (0, meaning no symptoms, to 16, meaning the most severe symptoms)
Time frame: Baseline/12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Drug | Interstitial Cystitis Problem Index (ICPI) | Baseline | 13.5 units on a scale | Standard Deviation 2.2 |
| Inactive Drug | Interstitial Cystitis Problem Index (ICPI) | Week 12 | 9.1 units on a scale | Standard Deviation 5.1 |
| Adalimumab | Interstitial Cystitis Problem Index (ICPI) | Baseline | 13.8 units on a scale | Standard Deviation 1.7 |
| Adalimumab | Interstitial Cystitis Problem Index (ICPI) | Week 12 | 9.9 units on a scale | Standard Deviation 3.6 |
Comparison: Statistical improvement in the adalimumab group compared to the placebo group from baseline to week 12.p-value: 0.7695% CI: [2.1, 5.8]t-test, 2 sided
Secondary
Interstitial Cystitis Symptom Index (ICSI)
Improvement in O'Leary Sant Interstitial Cystitis Symptom Index (ICSI) Total scores on a range scale: 0-20 (0, meaning no symptoms, to 20, meaning the most severe symptoms)
Time frame: Baseline/ 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Drug | Interstitial Cystitis Symptom Index (ICSI) | Baseline | 14.2 units on a scale | Standard Deviation 3.1 |
| Inactive Drug | Interstitial Cystitis Symptom Index (ICSI) | Week 12 | 10.5 units on a scale | Standard Deviation 5.7 |
| Adalimumab | Interstitial Cystitis Symptom Index (ICSI) | Baseline | 14.0 units on a scale | Standard Deviation 2.7 |
| Adalimumab | Interstitial Cystitis Symptom Index (ICSI) | Week 12 | 10.0 units on a scale | Standard Deviation 4.2 |
Comparison: Statistical improvement in the adalimumab group compared to the placebo group from baseline to week 12.p-value: 0.9995% CI: [1.7, 6.3]t-test, 2 sided
Secondary
Pelvic Pain Urgency/Frequency (PUF) Score
Pelvic Pain, Urgency/Frequency Symptom Scale Total scores on a scale range: 0-35 (0, meaning no symptoms, to 35, meaning the most severe symptoms)
Time frame: Baseline12 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inactive Drug | Pelvic Pain Urgency/Frequency (PUF) Score | Baseline | 24.2 units on a scale | Standard Deviation 3.9 |
| Inactive Drug | Pelvic Pain Urgency/Frequency (PUF) Score | Week 12 | 17.3 units on a scale | Standard Deviation 8.7 |
| Adalimumab | Pelvic Pain Urgency/Frequency (PUF) Score | Baseline | 24.6 units on a scale | Standard Deviation 4.1 |
| Adalimumab | Pelvic Pain Urgency/Frequency (PUF) Score | Week 12 | 18.3 units on a scale | Standard Deviation 6.9 |
Comparison: Statistical improvement in the adalimumab group compared to the placebo group from baseline to week 12.p-value: 0.7695% CI: [2.6, 10]t-test, 2 sided