Interstitial Cystitis
Conditions
Keywords
Interstitial Cystitis, urgency, frequency, MN-001, Global Response Assessment, bladder pain/urgency, O'Leary Sant IC Symptom and Problem Index
Brief summary
To evaluate the safety and efficacy of 8 weeks of treatment with MN-001 at 500 mg bid, 500 mg once daily vs. placebo in patients with Interstitial Cystitis.
Detailed description
This is a randomized, double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of two dosing regimens of MN-001 in patients with Interstitial Cystitis (IC). Patients will be screened for study eligibility within seven to nine days of randomization. Eligible patients will be randomized in a 1:1:1 ratio to receive either 500 mg MN-001 bid, 500 mg MN-001 once daily or placebo. Patients will be dispensed study drug beginning at Baseline (Visit 2) and will return to the study center for Visit 3 (28 days ± 2 days after Baseline), and Visit 4 (56 days ± 2 days after Baseline), at end of study for safety and efficacy assessments. The patient will be contacted by telephone at Week 6 (42 days ± 2 days after Baseline) for an interim follow up. Study drug will be dispensed at Visits 2 and 3. Safety assessments will include adverse events, physical examinations, clinical laboratory testing, and changes in vital signs. Efficacy assessments include percentage of patients at least moderately improved for each treatment group using the patient reported Global Response Assessment (GRA) (see Appendix 1). Secondary assessments include a decrease in bladder pain/urgency based on change in the patient rating from baseline to endpoint using the GRA (see Appendix 1), modified Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale (see Appendix 2) and the O'Leary Sant IC Symptom and Problem Index.
Interventions
DRUGMN-001 BID
Eligible patients received 500 mg MN-001 bid
DRUGMN-001
Eligible patients received 500 mg MN-001 once daily (qd)
DRUGPlacebo
Eligible patients received placebo
Sponsors
MediciNova
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 years of age with a diagnosis of moderate to severe IC; * Bladder pain ≥ 6 months prior to baseline; * Urinary frequency of ≥ 8 ≤ 30 micturitions within 24 hours while awake; * Nocturia ≥ 2x/night; * Males and females of child-bearing potential (not surgically sterile or post-menopausal) must be abstinent or agree to use an study-accepted contraceptive regimens throughout the study: * Female patients of child bearing age must have a negative urine pregnancy test at screening; * Must provide a signed informed consent.
Exclusion criteria
* Male or females \< 18 years of age; * Initiation of new IC medication ≤ 30 days prior to baseline; * Treatment with Elmiron ≤ 120 days prior to baseline; * Treatment with bladder hydro-distention ≤ 6 months prior to baseline; * Treatment with intravesical therapy ≤ 60 days prior to baseline; * History of previous procedure(s) (e.g., augmentation cytoplasty, cystectomy or cystolysis) that has affected bladder function; * Active genital herpes or vaginitis ≤ 90 days prior to baseline; * Urinary tract or prostatic infection ≤ 90 days prior to baseline; * History of urethral diverticulum; * History of bladder or ureteral calculi; * History of cyclophosphamide or chemical cystitis, urinary tuberculosis or radiation cystitis; * History of bladder tumors; * History of uterine, cervical, vaginal, prostatic or urethral cancer ≤ 5 years prior to baseline; * Patient is currently pregnant, lactating or likely to become pregnant during the study; * Participated in another clinical study with an investigational drug or device ≤ 30 days prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Subjects at Least Moderately Improved for Each Treatment Group in Patient Reported Global Response Assessment (GRA) | 8 weeks | The primary endpoint was the GRA overall change in their condition at Week 8. Each patient completed the questionnaire that rated the improvement in their IC symptoms based on responses to the GRA questions. Each question asked the patient to describe the OVERALL CHANGE in pain, urgency, frequency or overall change in their problem compared to the status before taking the study medication. Each parameter was rated on a 7 point scale: markedly worse, moderately worse, mildly worse, same, mildly improved, moderately improved and markedly improved. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders for GRA Assessment in Their Condition at Week 4. | 4 weeks | Responders were defined as patients who were 'moderately improved' or 'markedly improved' and non-responders were defined as patients who were 'markedly worse', 'moderately worse', 'mildly worse', no change, or 'mildly improved' on the GRA assessments. |
Countries
United States
Participant flow
Recruitment details
Patients were screened for study eligibility within 7-9 days of randomization. Patients underwent screening at Visit 1 (≤ 7 days prior to Baseline) and additional eligibility assessments prior to randomization at Visit 2 (Baseline Visit, Day 0).
Pre-assignment details
Eligible patients were randomized in a 1:1:1 ratio to receive 500 mg MN-001 twice daily (BID), 500 mg MN-001 once daily (QD), or placebo. Patients returned to the study center at Visit 3 (Day 28) and at Visit 4 (Week 8, Day 64) for safety and efficacy assessments. Patients were dispensed study drug at Baseline (Visit 2) and Visit 3.
Participants by arm
| Arm | Count |
|---|---|
| MN-001 500 mg qd This group received MN-001 500mg orally (PO)once a day. Patients underwent screening at Visit 1 (≤ 7 days prior to Baseline) and additional eligibility assessments at Visit 2 (Baseline Visit) prior to randomization and after randomization, were scheduled to return at Visit 3 (28 days ± 2 days after Baseline) and at Visit 4 (Week 8, 64 ± 2 days after Baseline) for safety and efficacy assessments. Patients were dispensed study drug at Baseline (Visit 2) and Visit 3. The patients were contacted by telephone at Week 6 (42 days ± 2 days after Baseline) for an interim follow up. | 95 |
| MN-001 500 mg BID Patients received MN-001 500 mg BID. Patients underwent screening at Visit 1 (≤ 7 days prior to Baseline) and additional eligibility assessments at Visit 2 (Baseline Visit) prior to randomization and after randomization, were scheduled to return at Visit 3 (28 days ± 2 days after Baseline) and at Visit 4 (Week 8, 64 ± 2 days after Baseline) for safety and efficacy assessments. Patients were dispensed study drug at Baseline (Visit 2) and Visit 3. The patients were contacted by telephone at Week 6 (42 days ± 2 days after Baseline) for an interim follow up. | 108 |
| Placebo Patients received placebo. Patients underwent screening at Visit 1 (≤ 7 days prior to Baseline) and additional eligibility assessments at Visit 2 (Baseline Visit) prior to randomization and after randomization, were scheduled to return at Visit 3 (28 days ± 2 days after Baseline) and at Visit 4 (Week 8, 64 ± 2 days after Baseline) for safety and efficacy assessments. Patients were dispensed study drug at Baseline (Visit 2) and Visit 3. The patients were contacted by telephone at Week 6 (42 days ± 2 days after Baseline) for an interim follow up. | 102 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 | 6 |
| Overall Study | did not continue to meet criteria | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Other | 3 | 5 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | required a prohibited medication | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 7 | 4 |
Baseline characteristics
| Characteristic | Total | MN-001 500 mg qd | MN-001 500 mg BID | Placebo |
|---|---|---|---|---|
| Age Continuous | 44 years STANDARD_DEVIATION 13.6 | 45.2 years STANDARD_DEVIATION 12.87 | 43.5 years STANDARD_DEVIATION 13.95 | 43.4 years STANDARD_DEVIATION 13.97 |
| diagnosis of moderate to severe interstitial cystitis (IC) with bladder pain for ≥ 6 months <=18 years | 0 participants | 0 participants | 0 participants | 0 participants |
| diagnosis of moderate to severe interstitial cystitis (IC) with bladder pain for ≥ 6 months Over 18 years old | 305 participants | 95 participants | 108 participants | 102 participants |
| Region of Enrollment United States | 305 participants | 95 participants | 108 participants | 102 participants |
| Sex: Female, Male Female | 271 Participants | 82 Participants | 97 Participants | 92 Participants |
| Sex: Female, Male Male | 34 Participants | 13 Participants | 11 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 92 | 65 / 105 | 28 / 99 |
| serious Total, serious adverse events | 1 / 92 | 0 / 105 | 1 / 99 |
Outcome results
Primary
Number Subjects at Least Moderately Improved for Each Treatment Group in Patient Reported Global Response Assessment (GRA)
The primary endpoint was the GRA overall change in their condition at Week 8. Each patient completed the questionnaire that rated the improvement in their IC symptoms based on responses to the GRA questions. Each question asked the patient to describe the OVERALL CHANGE in pain, urgency, frequency or overall change in their problem compared to the status before taking the study medication. Each parameter was rated on a 7 point scale: markedly worse, moderately worse, mildly worse, same, mildly improved, moderately improved and markedly improved.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MN-001 500 mg qd | Number Subjects at Least Moderately Improved for Each Treatment Group in Patient Reported Global Response Assessment (GRA) | 31 participants |
| MN-001 500 mg BID | Number Subjects at Least Moderately Improved for Each Treatment Group in Patient Reported Global Response Assessment (GRA) | 26 participants |
| Placebo | Number Subjects at Least Moderately Improved for Each Treatment Group in Patient Reported Global Response Assessment (GRA) | 30 participants |
Secondary
Number of Responders for GRA Assessment in Their Condition at Week 4.
Responders were defined as patients who were 'moderately improved' or 'markedly improved' and non-responders were defined as patients who were 'markedly worse', 'moderately worse', 'mildly worse', no change, or 'mildly improved' on the GRA assessments.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MN-001 500 mg qd | Number of Responders for GRA Assessment in Their Condition at Week 4. | 19 participants |
| MN-001 500 mg BID | Number of Responders for GRA Assessment in Their Condition at Week 4. | 26 participants |
| Placebo | Number of Responders for GRA Assessment in Their Condition at Week 4. | 12 participants |