Safety, Tolerability and Efficacy Study of LiRIS® 400 mg in Women With Interstitial Cystitis

A Phase 2 Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Evaluating Safety, Tolerability and Efficacy of LiRIS® 400 mg in Women With Interstitial Cystitis Followed by an Open Label Extension

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01824303

Enrollment

Registered

2013-04-04

Start date

2013-03-31

Completion date

2014-12-31

Last updated

2016-01-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Interstitial Cystitis

Brief summary

The purposes of the study is to determine if LiRIS®, an investigational drug-delivery system, is safe and tolerable in women with Interstitial Cystitis (IC), and to evaluate any change in IC symptoms following LiRIS administration.

Detailed description

The study is conducted in 2 parts: a randomized, blinded part in which subjects are assigned randomly (by chance) to LiRIS 400 mg or LiRIS placebo; subjects who complete this part and are eligible to continue, may participate in the open-label part in which all subjects receive LiRIS 400 mg. In both parts of the study (blinded and open-label), LiRIS is inserted into the bladder during cystoscopy, remains in the bladder for 14 days, and is removed during cystoscopy. In addition to the 14 day period with the LiRIS/LiRIS Placebo, there is a screening period of up to 2 weeks and a follow up period of 4 weeks.

Interventions

DRUGLiRIS 400 mg

LiRIS 400 mg contains lidocaine which is gradually released into the bladder over 14 days.

OTHERLiRIS Placebo

LiRIS Placebo contains lactose, inactive substance.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Blinded study: * Women age 18 and over * Diagnosed with Interstitial Cystitis as defined by protocol * Able to report IC symptoms of bladder pain, voiding habits, as required by protocol, and record in diary * Able to comply with visit schedule and diary completion at home Open-label Extension: * Must have completed the blinded study prior to screening for the Open-label extension

Exclusion criteria

(Blinded and Open-Label Extension): * Pregnant or lactating women * History or presence of any condition that would make it difficult to accurately evaluate bladder symptoms * Bladder or urethral abnormality that would prevent safe insertion of investigational product * Requiring medication not allowed per study protocol

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)	Baseline, Day 12	Participants rated their bladder pain over the previous 24 hours in an electronic diary using a horizontal line NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. Bladder pain was averaged over a period of 3 days. A negative change from Baseline indicates improvement.

Secondary

Measure	Time frame	Description
Change From Baseline in Night-Time Daily Voids	Baseline, Day 27	Participants recorded number of night-time daily voids in a 3 day Voiding Frequency electronic diary. The total number of night-time daily voids was averaged over a period of 3 days. A negative change from Baseline indicates improvement.
Change From Baseline in Average Void Volume Per Micturition	Baseline, Day 27	Participants recorded the amount of each void in millimeters (mL) in an electronic diary. The total amount of void per micturition (each void) was averaged over a period of 24 days. A negative change from Baseline indicates improvement.
Change From Baseline in Post-Void Bladder Pain	Baseline, Day 27	Participants rated their bladder pain immediately completing voiding in an electronic diary using a horizontal line NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. The average of the data from the first 5 voids prior to Baseline and the 3 days prior to Day 12 were averaged for analyses. A negative change from Baseline indicates improvement.
Change From Baseline in Total Daily Voids	Baseline, Day 27	Participants recorded number of daily voids (day-time and night-time daily voids) in a 3 day Voiding Frequency electronic diary. The total number of daily voids was averaged over a period of 3 full days. A negative change from Baseline indicates improvement.
Change From Baseline in O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) Score	Baseline, Day 27	The ICPI is a participant reported questionnaire to rate their problems in the following 4 areas: Frequent urination; Getting up at Night to Urinate: Urination with little warning; Burning pain and discomfort. Questions are answered on a 5-point scale where: 0=No Problem to 4=Big Problem. The total score is the sum of the individual scores for a total possible score of 0 (best) to 20 (worst). A negative change from Baseline indicates improvement.
Change From Baseline in Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS)	Baseline, Day 27	The BPIC-SS is a participant reported questionnaire consisting of 8 items. Questions (Q) 1-5 (How often urination because of pain; Need to urinate after just urinating; How often urination to avoid worse pain; How often feeling of pressure in bladder; How often pain in bladder) answered on a 5-point scale where: 0=Never to 4=Always. Q 6-7 (Bothered by frequent Day-time urination; Bothered by Night-time urination) answered on a 5-point scale where: 0=Not At All to 4=A Great Deal. Q8 (pain) rated on a NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. The Total Score is the sum of the individual questionnaire of all 8 items for a total possible score of 0 (best) to 38 (worst). A negative change indicates improvement.
Change From Baseline in Brief Pain Inventory (BPI)	Baseline, Day 27	The BPI is a 7-item participant completed questionnaire. The participant answered questions as to how pain interfered with: General Activity, Mood, Walking Ability, Normal work, Relations with other people, Sleep and Enjoyment of life. Questions were answered on an 11-point scale where: 0=Does not interfere to 10=Completely interferes. The total score is the average of the individual questionnaire items for a total possible score of 0 (best) to 10 (worst). A negative change from Baseline indicates improvement.
Change From Baseline in O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) Score	Baseline, Day 27	The ICSI is a participant reported questionnaire to rate their symptoms by answering 4 questions. Question (Q) 1 and 2 (urine urgency) using a 6-point scale where: 0=Not at All to 5=Almost Always. Q3 (night-time voids) using a 6-point scale where: 0=None to 5=5 or More Times. Q4 (pain and burning) using a 6-point scale where: 0=Not at All to 5=Usually. The total score is the sum of the individual scores for a total possible score of 0 (best) to 20 (worst). A negative change from Baseline indicates improvement.

Countries

Canada, United States

Participant flow

Pre-assignment details

31 participants signed the informed consent form and were enrolled in the study, 30 participants had the investigational product inserted and are included the Intent-to-treat Population.

Participants by arm

Arm	Count
LiRIS 400 mg LiRIS 400 mg: investigational drug-delivery system which contains Lidocaine; the system remains in the bladder for 14 days.	16
LiRIS Placebo LiRIS Placebo: investigational drug-delivery system which contains Lactose and no Lidocaine; the system remains in the bladder for 14 days.	14
Total	30

Withdrawals & dropouts

Period	Reason	FG000	FG001
Randomized Study	Other Miscellaneous Reasons	1	0
Randomized Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	LiRIS 400 mg	LiRIS Placebo	Total
Age, Continuous	41.7 years STANDARD_DEVIATION 14.13	42.1 years STANDARD_DEVIATION 10.54	41.9 years STANDARD_DEVIATION 12.37
Sex: Female, Male Female	16 Participants	14 Participants	30 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	11 / 16	12 / 14	6 / 12	6 / 11
serious Total, serious adverse events	0 / 16	0 / 14	0 / 12	0 / 11

Outcome results

Primary

Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)

Participants rated their bladder pain over the previous 24 hours in an electronic diary using a horizontal line NRS by putting a mark on the line where: 0 (the far left of the line)=no pain to 10 (far right of the line)=worst pain imaginable. Bladder pain was averaged over a period of 3 days. A negative change from Baseline indicates improvement.

Time frame: Baseline, Day 12

Population: Intent-to-treat (ITT) population included all randomized participants.

Arm	Measure	Group	Value (MEAN)	Dispersion
LiRIS 400 mg	Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)	Baseline	7.04 unit on a scale	Standard Deviation 0.75
LiRIS 400 mg	Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)	Change from Baseline at Day 12	-1.44 unit on a scale	Standard Deviation 1.584
LiRIS Placebo	Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)	Baseline	7.67 unit on a scale	Standard Deviation 1.067
LiRIS Placebo	Change From Baseline in Participant Reported Average Bladder Pain on a Numerical Rating Scale (NRS)	Change from Baseline at Day 12	-2.50 unit on a scale	Standard Deviation 2.723

Secondary

Change From Baseline in Average Void Volume Per Micturition

Participants recorded the amount of each void in millimeters (mL) in an electronic diary. The total amount of void per micturition (each void) was averaged over a period of 24 days. A negative change from Baseline indicates improvement.

Time frame: Baseline, Day 27