Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

Brief Title

Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

Official Title

Understanding the Long-Term Management of Organic Acidemia Patients With CARBAGLU®: A Mixed Methods Approach

Brief Summary

      This is a prospective mixed-design study focused on the long-term management of propionic
      aciduria (PA) and methylmalonic aciduria (MMA) with N-carbamylglutamate (NCG) maintenance
      therapy. Treatment characteristics, clinical outcomes, and healthcare utilization data of
      patients diagnosed PA or MMA treated >6 months therapy with NCG are collected at baseline, 12
      months, and 18 months. Qualitative interviews with adult patients and caregivers are
      conducted >6 months after study enrollment to gain a better understanding of the disease
      burden and the treatment burden of patients and their families.

Detailed Description

      Study Design: This is a prospective, longitudinal, observational study of patients diagnosed
      with organic acidemia that has been on treatment with carglumic acid for a minimum of six
      months for the long-term management of their disease. This prospective observational study
      population will include up to 40 diagnosed MMA or PA patients with current carglumic acid
      treatment experience from 6 European countries: Sweden, the United Kingdom (UK), the
      Netherlands, Germany, Norway, Italy, Spain and France. The patients (or caregivers) included
      in this prospective observational study will also be invited to participate in a one-on-one
      phone interview.

      Study Procedures: After Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
      approval is obtained for the protocol and all supporting protocol documents, clinicians
      caring for patients with MMA or PA will provide their patients (or caregivers) with the
      opportunity to participate in the study. Patients (or caregivers) will receive an Information
      Letter (PIL) (Appendices A and B) inviting them (or their caregiver) to take part in a
      prospective observational study and in a one-on-one phone interview.

      Patients (or caregivers) who are interested in participating in this observational/interview
      study will review the informed consent form (Appendices C and D) with the clinician and
      his/her research team. If agreeable, patients (or caregivers) will be asked to sign the
      consent form and a countersigned copy will be provided to them for their records. Clinicians
      and their research team at each site will then review patient charts and record demographic
      and medical history information for each patient. Patient information from medical charts
      will be collected at the start of the study (baseline), and 12 months and 18 months after
      baseline. All information derived from medical chart reviews will be recorded through
      web-based Electronic Data Capture system (EDC).

      Patients (or caregivers) who agree to participate in a one-on-one phone interview will
      provide contact information for their clinicians and the respective research team to include
      in the Contact Information Form (CIF) (Appendix E). Researchers will then contact patients
      (or caregivers) directly to schedule a one-hour phone interview. An interview guide
      (Appendices F and G) including open-ended questions and probes will be used to elicit
      concepts and orient the discussion during the interview. Patient (or caregiver) interviews
      will focus on describing the symptoms and impacts of MMA or PA, as well as patient treatment
      experiences with carglumic acid, their treatment preferences, and their satisfaction with
      treatment. At the end of the interview, patients (or caregivers) will be asked to complete a
      Demographic and Health Information Form (DHIF; Appendices H and I). Phone interviews will be
      audio-recorded with the patient's (or caregiver) permission, transcribed and translated (as
      needed) in preparation for qualitative analysis.

      Data Analysis: The primary prospective data analysis will involve a comparison of the
      incidence and duration of decompensation episodes pre- and post- initiation of carglumic
      acid. Additional analysis will include healthcare resource utilization around individual
      decompensation events, patient/caregiver burden, and patient/caregiver satisfaction with
      treatment. All prospective data will be undertaken using SAS® software, version 9.4 of the
      SAS® system for Windows (Cary, NC, USA). All qualitative data from the interviews will be
      analyzed using ATLAS.ti, a software package uniquely designed to analyze qualitative data.
      The audio-recorded verbatim transcripts of the interviews will be coded to identify patterns
      in participants' responses concerning patient experiences with the symptoms and impacts of
      MMA or PA, treatment experience with carglumic acid, patient treatment preferences, and
      treatment satisfaction. Findings will be summarized in a final report and may be published or
      presented by the investigator(s) after the review by, and in consultation and agreement with,
      the sponsor. If published or presented, the results will be presented in such a way that
      confidential or proprietary information is not disclosed.

Study Type


Primary Outcome

Change in Number and Duration of Decompensation Events

Secondary Outcome

 Frequency and Duration of Healthcare Resource Utilization


Methylmalonic Acidemia


Carglumic Acid

Study Arms / Comparison Groups

Description:  Patients with confirmed diagnosis of methylmalonic acidemia, and treated with carglumic acid, at any dose form, any dosage,


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 15, 2019

Completion Date

December 15, 2021

Primary Completion Date

June 15, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has confirmed diagnosis of an organic acidemia (e.g., MMA or PA)

          2. Patient initiated treatment with carglumic acid for long-term management of MMA or PA

          3. Patient has been treated with carglumic acid for a minimum of 6 months

          4. Patient (or caregiver) is able to comply with all prospective study procedures

          5. Patient (or caregiver) is able to provide informed consent

        Exclusion Criteria:

          -  None




6 Months - 99 Years


Sufin Yap, MD, 33 1 79911282, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Recordati Rare Diseases

Study Sponsor

Sufin Yap, MD, Principal Investigator, Sheffield Children's NHS Trust

Verification Date

January 2020