A Study of Pentosan Polysulfate Sodium and the Development of Pigmentary Maculopathy and Pigmentary Retinopathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate incidence and prevalence rates of the study endpoints (pigmentary maculopathy [PM]/ pigmentary retinopathy [PR]/Any, PM/PR/ pentosan polysulfate sodium [PPS], and PM/PR/Non-PPS) in relation to PPS exposure, and in participants with interstitial cystitis (IC) but not exposed to PPS; changes in visual acuity (VA) over time; participant treatment journey leading to PPS treatment, and potential risk factors associated with the occurrence of PM/PR/PPS.

Official Title
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Post-authorization Safety Study and Real-world Evaluation of the Use of Pentosan Polysulfate Sodium and the Development of Pigmentary Maculopathy and Pigmentary Retinopathy

Conditions
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Pigmentary Maculopathy, Pigmentary Retinopathy, Interstitial Cystitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have at least 6 months baseline information prior to index date (this may apply to the relevant databases, if the study participants are identified and the outcomes are ascertained via multiple linked data source) For the pentosan polysulfate sodium (PPS) Cohort Participants must have records in both the intelligent research in sight (IRIS) database and the closed claims portion of the Komodo claims database and have at least one record of PPS dispensing For the interstitial cystitis (IC) Cohort not exposed to PPS Participants must have records in both the IRIS database and the closed claims portion of the claims database; have at least one diagnosis of IC; and have no record of PPS dispensing Exclusion Criteria: - Evaluated based on the Komodo database. Participants will be excluded from the study if they have no information on age or sex (or both)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Clean Cohort<br>Clean cohort refers to cohort of participants who had their first documented exposure to pentosan polysulfate sodium (PPS; Elmiron) on or after 22 May 2018 and who are assumed to have had shorter exposure (the earliest available data based on the linked database between the IRIS registry and Komodo database in this study). | |
| Overall Cohort<br>Overall cohort refers to cohort of participants who had their first documented exposure to PPS (Elmiron) any time beginning 01 January 2015 and who are assumed to have relatively longer exposure (the earliest available data based on the linked database between the intelligent research in sight (IRIS) registry and Komodo database in this study). | |
| Interstitial Cystitis (IC) Cohort<br>IC cohort refers to cohort of participants who had at least one IC diagnosis beginning 01 January 2015 and had no documented exposure to PPS based on the records from the Komodo database (the earliest available data based on the linked database between the IRIS registry and Komodo database in this study). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clean Cohort: Incidence Rate of Pigmentary Maculopathy (PM)/ Pigmentary Retinopathy (PR)/Any Cases | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants exposed to pentosan polysulfate sodium [PPS]). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases divided by number of person-years time at risk. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Incidence Rate of PM/PR/PPS | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants exposed to PPS). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases divided by number of person-years time at risk. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Incidence Rate of PM/PR/Non-PPS | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants not exposed to PPS). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases divided by number of person-years time at risk. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Prevalence Rate of PM/PR/Any Cases | Prevalence rate is defined as number of prevalent cases per number of target cohort assessed (example, number of participants exposed to PPS). | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Prevalence Rate of PM/PR/PPS | Prevalence rate is defined as number of prevalent cases per number of target cohort assessed (example, number of participants exposed to PPS). | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Prevalence Rate of PM/PR/Non-PPS | Prevalence rate is defined as number of prevalent cases per number of target cohort assessed (example, number of participants not exposed to PPS). | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Overall Cohort: Incidence Rate of PM/PR/Any Cases | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants exposed to pentosan polysulfate sodium [PPS]). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases divided by number of person-years time at risk. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Prevalence Rate of PM/PR/Any Cases | Prevalence rate is defined as number of prevalent cases per number of target cohort assessed (example, number of participants exposed to PPS). | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Incidence Rate of PM/PR/PPS | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants exposed to pentosan polysulfate sodium [PPS]). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases divided by number of person-years time at risk. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Prevalence Rate of PM/PR/PPS | Prevalence rate is defined as number of prevalent cases per number of target cohort assessed (example, number of participants exposed to PPS). | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Number of PM/PR/PPS Cases Among the PM/PR/Any Cases | Number of PM/PR/PPS cases among the PM/PR/any cases will be reported. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Clean Cohort: Change in Visual Acuity (VA) in Relation to PPS Dose | Change in VA in relation to PPS dose will be reported. It will be assessed based on the following categories: a) No change (refers to less than [<] 1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) greater than or equal to (>=) 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Change in VA in Relation to PM/PR/Any Cases | Change in VA in relation to study endpoint (PM/PR/Any) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohort: Change in VA in Relation to PM/PR/PPS | Change in VA in relation to study endpoint (PM/PR/PPS) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Clean Cohorts: Change in VA in Relation to PM/PR/Non-PPS | Change in VA in relation to study endpoint (PM/PR/Non-PPS) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 22-May-2018 to 31-Mar-2021 will be examined | 
| Overall Cohort: Change in Visual Acuity (VA) in Relation to PPS Dose | Change in VA in relation to PPS dose will be reported. It will be assessed based on the following categories: a) No change (refers to less than [<] 1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) greater than or equal to (>=) 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Change in VA in Relation to PM/PR/Any Cases | Change in VA in relation to study endpoint (PM/PR/Any) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Change in VA in Relation to PM/PR/PPS | Change in VA in relation to study endpoint (PM/PR/PPS) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Overall Cohort: Change in VA in Relation to PM/PR/Non-PPS | Change in VA in relation to study endpoint (PM/PR/Non-PPS) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Interstitial Cystitis (IC) Cohort: Incidence Rate of PM/PR/Any Cases Among the Participants with IC and No-Exposure to PPS | Incidence rate is defined as number of incident cases per number of all participants at risk (that is, number of all participants not exposed to PPS). Incidence rate is calculated by using formula: incidence rate (per 100 person-years)= number of incidence cases per number of person-years time at risk. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| IC Cohort: Change in VA in Relation to PM/PR/Any Cases | Change in VA in relation to study endpoint (PM/PR/Any) will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| IC Cohort: Change in VA Based on Age | Change in VA based on age among participants exposed to PPS and without exposure to PPS will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| IC Cohort: Change in VA Based on Sex | Change in VA based on sex among participants exposed to PPS and without exposure to PPS will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| IC Cohort: Change in VA Based on Time Between the First and Last VA Measurement in Matched Cohorts | Change in VA based on time between the first and last VA measurement in matched cohorts among participants exposed to PPS and without exposure to PPS will be reported. It will be assessed based on the following categories: a) No change (refers to <1 line of worsening or improvement, considered not clinically meaningful); b) 1 to <3 lines of worsening; c) >= 3 lines of worsening; d) 1 to <3 lines of improvement; e) >= 3 lines of improvement. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic characteristics of Cohorts: Age | Demographic characteristics of cohorts (age) will be reported. | Baseline | 
| Demographic characteristics of Cohorts: Sex | Demographic characteristics of cohorts (sex) will be reported. | Baseline | 
| Demographic characteristics of Cohorts: Race | Demographic characteristics of cohorts (race including Asian, black or African American, other, White or Caucasian) will be reported. | Baseline | 
| Demographic characteristics of Cohorts: Ethnicity | Demographic characteristics of cohorts (ethnicity including Hispanic and non-Hispanic) will be reported. | Baseline | 
| Number of Participants with Comorbidities | Number of participants with general comorbidities (diabetes, hypertension, hypercholesterolemia, vaginitis, urinary tract infection [UTI], detrusor instability, urge incontinence, and overactive bladder, autoimmune disease, Malignant tumor(s) of head and neck [plus documentation of radiation therapy] and Radiation cystitis) and ocular comorbidities (diabetic retinopathy, diabetic macular edema, optic neuropathy, glaucoma, glaucoma-related procedure, cataract [diagnosis], cataract [procedure]) will be reported. | Baseline | 
| Number of Participants who had Provider Characteristics | Number of participants who had provider characteristics (treating provider specialty [retina specialist, non-retina specialist, general ophthalmologist, optometrist]; rural or non-rural location of index practice [rural/non-rural; United States Department of Agriculture Economic research service 2010 classification]) will be reported. | Baseline | 
| Overall Cohort: Distribution of International Classification of Diseases (ICD)-9/10 Codes | ICD-9/10 codes are compared among the participants who are exposed to PPS will be reported. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined | 
| Participant's Journey to PPS | Participant's journey to PPS is defined as the sequence of medications and other interventions the participant received before and after receiving PPS. | Data analysed retrospectively from 01-Jan-2015 to 31-Mar-2021 will be examined |