Phase IV to Evaluate the Safety of Self-administered ADASUVE® in Agitated Patients Outside the Hospital Setting
Condition: Agitation
MeSH terms: Psychomotor Agitation
Study type: Interventional
Phase: Phase 4

Summary: 
      Phase IV, multinational, multicentre, open-label, non-randomized, clinical trial conducted in
      Europe (Spain, Germany, Finland, Norway, Romania and Austria) to evaluate the safety profile
      of ADASUVE® in agitated patients with schizophrenia or bipolar disorder when
      self-administered outside of a hospital setting without the supervision of a healthcare
      professional. The Study will aim to include approximately 500 patients who have been
      previously treated with ADASUVE® in the last 6 months prior to screening or recently treated
      during the planned recruitment period of 6 months with a 'positive outcome' ('ADASUVE®
      responder') according to Clinical Global Impressions (CGI-I) scale, from a total of about
      30-34 centers. All patients will be followed up for a maximum of 6 months from baseline,
      during which it is expected that a new episode of agitation will occur.
    

Detailed description: 
      OVERALL STUDY DESIGN:

      This is a phase IV, multinational, multicentre, open-label, non-randomized, clinical trial
      conducted in Europe (Spain, Germany, Finland, Norway, Romania and Austria) to evaluate the
      safety profile of ADASUVE® in agitated patients with schizophrenia or bipolar disorder when
      self-administered outside of a hospital setting without the supervision of a healthcare
      professional.

      The Study will aim to include approximately 500 patients who have been previously treated
      with ADASUVE® in the last 6 months prior to screening or recently treated during the planned
      recruitment period of 6 months with a 'positive outcome' ('ADASUVE® responder') according to
      Clinical Global Impressions (CGI-I) scale, from a total of about 30-34 centers. An 'ADASUVE®
      responder' is defined as having a CGI-I score at 2 hours after administration of either a 1
      (very much improved) or 2 (much improved). All patients will be followed up for a maximum of
      6 months from baseline, during which it is expected that a new episode of agitation will
      occur.

      Centers will be selected and qualified primarily based on their estimated number of eligible
      patients. The patients attending a hospital setting, such as Hospital Wards, Emergency Rooms,
      Day Care Units, Hospital Home-care units, or other Institutions for an agitation episode
      treatment will be recruited.

      Site study staff will screen patients for potential participation on the clinical study at
      the time of presentation in a hospital setting for an on-going agitation episode during the
      recruitment period of 6 months, or retrospectively for a previous one episode within the 6
      months prior to screening. The study staff will review the patient's medical records in
      detail to determine eligibility.

      There will be a baseline hospital visit within 2 to 4 weeks after the screening for all
      pre-selected patients. This hospital visit will be scheduled after the resolution of the
      episode in patients pre-selected during an on-going agitation episode. Patients with a
      previous agitation episode will be called by phone by site staff for ensuring that they meet
      the eligibility requirements for enrolling and planning a baseline visit.

      At screening patients and family (or caregivers) will be informed by the study staff that at
      the baseline visit they will receive a specific training session for the proper
      self-administration of ADASUVE® outside the hospital setting and about other procedures
      related to the study.

      At the baseline visit, selected patients will be asked to provide the signed informed consent
      for inclusion in the study before any study related procedures.

      Once the informed consent has been obtained the eligibility criteria will be confirmed
      (including a negative result of the urine pregnancy test performed in women of childbearing
      potential and that the family member or other caregiver support is in place) for the patient
      inclusion.

      Once the patient is included in the study:

        -  He/she will receive one unit of ADASUVE® for treating the next agitation episode outside
           the hospital setting (plus a short-acting beta-agonist bronchodilator for treatment of
           possible severe respiratory side effects [i.e bronchospasm]).

        -  Patients with the presence of a family member or other caregiver will receive a specific
           training session for properly self-administration of ADASUVE® outside the hospital
           setting and clear indications to identify the appearance of an agitation crisis, based
           on the recognition of their escalating symptoms experienced in previous agitation
           episodes.

        -  Additional educational material will be provided to the patients in a document
           including:

           o Patient information card for recognition of symptoms of agitation, instructions of the
           study, information for recognition of respiratory symptoms and instruction of use of the
           medicine to treat them.

        -  The patient's diary card will be also delivered to the patient (and family
           member/caregiver).

        -  Patient will be trained to use the patient' diary card to register the agitation episode
           information.

      Each patient included in the study will receive a study kit containing: one unit ADASUVE® for
      the next agitation episode (plus a short-acting beta-agonist bronchodilator as rescue
      medication to treat severe respiratory symptoms), the instructions for the use of ADASUVE®,
      ADASUVE® storage instructions, the patient's diary card and the educational material. The
      patient's kit will also include useful instructions of ADASUVE® storage such as to store
      locked in a cool, dry place away from direct sunlight, to keep it out of reach of children,
      not to use it after the expiry date which is stated on the product label, not to discard it
      in the household waste and to keep it in pouch until time of use.

      At baseline the following data will be obtained retrospectively from medical records for each
      patient and will be recorded in the electronic case report forms: demographics, diagnosis,
      agitation information of current/previous episode (date/time of the onset, time to
      improvement and patient status rate at 2h of ADASUVE® administration [CGI-I scale]),
      respiratory disease history and risks factors, co morbidities/medical history
      (non-respiratory), concomitant medications, previous ADASUVE® treatment (date and dosing
      data).

      During the 6-month follow-up from baseline visit study staff will conduct a 10-minutes
      phone-calls (every 3 months approximately) to the enrolled patients or their family
      member/caregiver. Patients (or family member/caregiver) will be asked for general patient
      health status. In addition, patients will be reminded to return the medication if they have
      not presented a new episode of agitation after the 6 months of follow-up from the baseline
      visit. All these patients will be scheduled for the study staff for an end of study visit
      with the aim to return the unused study kit. These patients will be excluded from the study.
      All this related information will be recorded in the electronic case report forms.

      Three clinical scenarios can occur following the self-administration of ADASUVE® outside the
      hospital setting for the treatment of an acute agitation episode:

      • If there is an improvement within 2-hours post-dose self-administration of ADASUVE® outside
      the hospital setting and once the episode of acute agitation has dismissed, the following
      data will be collected at patient's diary card with adequate family (or caregiver) support:

      o Date of the diary completion, person who completed the diary (patient, relatives or
      caregiver), date/time of the onset of current episode of agitation, date/time of ADASUVE®
      self-administration, , severity of the episode (CGI-S scale) before ADASUVE® administration
      and time/rate to improvement of current episode of agitation (CGI-I scale) scores at 2, 10,
      20, 30, 60 and 120 minutes after ADASUVE® administration, AEs related to ADASUVE® during the
      following 24 hours of the self-administration, medications to treat ADASUVE®
      treatment-emergent AEs (e.g., short-acting bronchodilator) and another medication used
      following 24 hours of ADASUVE® administration.

      Once ADASUVE® treatment has taken place, immediately patient (or a family member/caregiver)
      must inform the corresponding study investigator to schedule a follow-up hospital visit
      (within 24-72h after ADASUVE® self-administration). The 24-72h follow-up visit after ADASUVE®
      self-administration with the study investigator will include a review of data from patient
      diary card that will be recorded in the electronic case report forms by the investigator
      staff. Additionally, the study investigator will confirm during the visit that the patient is
      in good general health based on their judgment and patients will be asked to evaluate their
      treatment satisfaction after self-administered ADASUVE® outside the hospital setting using a
      5-point Likert scale.

        -  If there is no improvement or worsening of the agitation after 1 hour of ADASUVE®
           self-administration outside the hospital setting, the patient must attend the assigned
           hospital for a 2nd dose of ADASUVE® (≥ 2 hours after dose one) or another medication to
           treat the agitation episode, at the discretion of the investigator. If additionally, the
           patient had reported an AE after the first administration of ADASUVE® outside the
           hospital setting and a second dose of ADASUVE® cannot be administered, another
           medication should be dispensed at hospital setting to treat this agitation episode.

        -  If after ≥2 hours of ADASUVE® self-administration outside the hospital setting there is
           a worsening of the agitation episode (once there was a previous improvement within
           2-hours post-dose administration), the patient must attend the assigned hospital for a
           2nd dose of ADASUVE® or another medication to treat the agitation episode, at the
           discretion of the investigator.

      The following data until discharge will be collected in the electronic case report forms by
      study staff if there is no improvement or worsening after self-administration of ADASUVE® for
      patients attending the hospital:

        -  Other treatments administered for agitation episode in addition to 1st dose of ADASUVE®
           self-administered outside the hospital setting or to the 2nd dose of ADASUVE® at
           hospital administration for non-responders patients (number and timing of doses
           administered)

        -  Other treatments administered for agitation in addition to 2nd dose of ADASUVE®.

        -  Date/time of the onset of current episode of agitation

        -  Time to onset of improvement of current episode

        -  AEs related to ADASUVE®

        -  Medications and/or interventions to treat ADASUVE® treatment-emergent AEs

        -  Status at discharge (admission to hospital, discharge to home or other facility, ongoing
           hospitalization, leave against medical advice, other) All these patients who
           self-administered ADASUVE® outside the hospital setting should return the used study kit
           at the scheduled visit accordingly.

      Furthermore, patients will receive a follow-up call at 30 days after the self-administration
      of ADASUVE® outside the hospital setting to record the general health status of the patient
      including information about any other AEs related to ADASUVE® experienced during this period.
    

Intervention name(s): Staccato® Delivery System Loxapine (ADASUVE®)
Intervention type(s): Device
Intervention description(s): one dose Loxapine Staccato 9.1 mg
Other intervention name(s): ADASUVE®
Intervention MeSH terms: Loxapine
Intervention model: Single Group Assignment
Intervention model description: Intervention: treatment with Loxapine staccato- just one treatment arm - outside the hospital setting.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; bipolar disorder