Nervous System DiseasesPhase 3NCT03336645
Open-label Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Children With Status Epilepticus (Convulsive) in a Healthcare Setting in Japan
A Phase 3 study testing SHP615 in people with Nervous System Diseases, run by Shire at 23 sites in Japan.
Trial summary
The purpose of this study is to assess the efficacy, safety and pharmacokinetics of MHOS/SHP615 administered buccally in children with status epilepticus (convulsive) in a healthcare setting. Read more about this study
- Who is it for?
- Ages 3 to 216 months
- Conditions the study is for
- Nervous System Diseases
- What is being tested?
- SHP615
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 23 sitesJapan
- Study dates
- 23 Oct 2017to 19 Aug 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 216 months
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female participants whose corrected gestational age is greater than or equal to (>=) 52 weeks (gestational weeks plus the number of weeks after birth) and less than (<) 18 years (and weight greater than [>] 5 kilogram [kg]), at the time of investigational product administration. If the participant's exact age is not known, the participant should be excluded.
- Parent, guardian, or legally authorized representative (LAR) of the child provides informed consent (and assent, when applicable per Shire policy and country regulations) to participate in the study prior to participation in any protocol specific procedures. The participant may be prescreened by the investigator in their clinical practice and the parent, guardian, or LAR may sign informed consent before the participant presents to the healthcare setting for treatment of the seizure.
- Participant with generalized tonic-clonic SE with seizures accompanied by loss of consciousness with any of the following characteristics persistent at the time of study drug administration:
- Currently presenting with seizure (convulsive) activity and 3 or more convulsions within the preceding hour
- Currently presenting with seizure (convulsive) and 2 or more convulsions in succession without recovery of consciousness
- Currently presenting with a single seizure (convulsive) lasting >=5 mins
Who cannot join
- Female participants who are pregnant, suspected to be pregnant, or nursing.
- Subjects with major trauma, not necessarily restricted to the head, as the cause of the seizure.
- Subjects with seizures due to illegal drug or acute alcoholic intoxication.
- Subjects with known or suspected recurrent seizures due to illegal drug or alcohol withdrawal.
- Subjects with history of seizures of psychogenic origin.
- Subjects with seizures due to severe encephalitis or meningitis, as determined by the PI
Show all 17Show fewer
- Subjects with known history of hypersensitivities, non-responsiveness or contraindications to benzodiazepines (ie, clinically significant respiratory depression, severe acute hepatic failure, myasthenia gravis, syndrome of sleep apnea, glaucoma with closed angle, use of concomitant drugs determined by the investigator to have a contraindication to the use of benzodiazepines.)
- Subjects with a known history of benzodiazepine abuse.
- Subjects who, in the judgment of the healthcare provider, have not responded to previous administrations of midazolam systemic therapies, including Midafresa and/or Dormicum.
- Subjects who need emergent surgical intervention and general anesthesia/intubation.
- Subjects with significant hypotension and cardiac dysrhythmia (example [eg], atrioventricular [AV] block of second or third degree, VT [ventricular tachycardia]).
- Subjects who have been receiving human immunodeficiency virus (HIV) protease inhibitors or HIV reverse transcriptase inhibitors.
- Subjects with current hypoglycemia (glucose <60 milligram per deciliter [mg/dL]) upon presentation at the hospital or healthcare setting.
- Subjects with severe cerebral anoxia (except cerebral palsy), in the judgment of the healthcare provider.
- Subjects have used an investigational product or been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
- Subjects has received antiseizure medication prior to arrival in the healthcare setting.
- Subjects has prior placement of a vagus nerve stimulator.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Japan23 sites
Fukuoka Children's Hospital(NW)
Fukuoka, 813-0017
Gifu Prefectural General Medical Center
Gifu, Gifu, 500-8717
NHO Hokkaido Medical Center
Hokkaidō, 063-0005
Yamanashi Prefectural Central Hospital
Kofu, Fujimi, 400-8506
Kumamoto Saishunso National Hospital
Kumamoto, 861-1196
NHO Nagasaki Medical Center
Nagasaki, 856-8562
NHO Nishi Niigata Chuo National Hospital
Niigata, 950-2085
Aichi Children's Health and Medical Center(NW)
Ōbu, 474-8710
NHO Minami-Okayama Medical Center
Okayama, Okayama-ken, 701-0304
Okayama University Hospital
Okayama, 700-0914
Nakano Children's Hospital
Osaka, 535-0022
Osaka Women's and Children's Hospital(NW)
Osaka, 594-1101
Saitama Children's Medical Center(NW)
Saitama, 330-8777
Jichi Children's Medical Center Tochigi
Saitama-shi, Saitama, 330-8503
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
Shizuoka Institute of Epilepsy and Neurological Disorders
Shizuoka, Shizuoka, 420-8688
Osaka University Hospital
Suita, 565-0871
Tokyo Women's Medical University Hospital
Tokyo, Kawadacho, 162-8666
National Center Hospital, NCNP
Tokyo, 187-0031
Tottori University Hospital
Tottori, 683-8504
Tokyo Women's Medical University Yachiyo Medical Center
Yachiyo, Owada Shinden, 276-8524
Osaka University Hospital
Yamadaoka, 565-0871
Kanagawa Children's Medical Center(NW)
Yokohama, 232-0066
About this study
Official title: A Phase 3, Multicenter, Open-label Study to Determine the Efficacy, Safety, and Pharmacokinetics of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in the Hospital or Emergency Room
The purpose of this study is to assess the efficacy, safety and pharmacokinetics of MHOS/SHP615 administered buccally in children with status epilepticus (convulsive) in a healthcare setting.
- Conditions
- Nervous System Diseases
- Being tested
- SHP615
- Keywords
- Seizure, Midazolam hydrochloride, Convulsive
- Medical subject headings
- Nervous System Diseases, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHP615Drug
Also called Midazolam hydrochloride oromucosal solution, MHOS
SHP615 oromucosal solution will be administered as a single age-specific dose (2.5, 5, 7.5 and 10 mg).
| Study group | Role | What they receive |
|---|---|---|
| SHP615 | Experimental | Participants will receive a single age-specific dose (approximately 0.25 to 0.5 milligram per kilogram [mg/kg] as midazolam) of SHP615 oromucosal solution through buccal route upon onset of seizures. Receives: Drug: SHP615 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Response Rate
Response rate was defined as the percentage of participants with therapeutic success. Therapeutic success was defined as the cessation of visible seizure activity within 10 minutes with a sustained absence of visible seizure activity for 30 minutes following a single dose of MHOS/SHP615 without the need for additional rescue medication.
Measured: From start of study drug administration up to 30 minutes post-dose
Secondary outcomes (18)
Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours
Percentage of participants whose seizure event stopped within 10 minutes of single dose administration of SHP615 and who had sustained absence of seizure activity for at least 1, 4, and 6 hours were reported.
Measured: From start of study drug administration up to 1, 4 and 6 hours post-dose
Number of Participants With Time to Resolution of Seizures (Convulsions)
Time to resolution of seizures (convulsions) was calculated as time from IP administration to the end of the initial seizure or administration of rescue anti-convulsant medication, whichever occurs first. Initial seizure referred to the seizure that triggered the use of the IP. Number of participants with time to resolution of seizures (convulsions) from the administration of SHP615 were reported.
Measured: From start of study drug administration up to follow-up (Day 8)
Number of Participants With Time to Recovery of Consciousness
Time to recovery of consciousness (in minutes) was calculated only for participants who lost consciousness pre-dose at time from investigational product administration to recovery of consciousness post-dose or administration of rescue anticonvulsant medication, whichever occurs first. Number of participants with time to recovery of consciousness were reported.
Measured: From start of study drug administration up to follow-up (Day 8)
Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)
Percentage of participants who required additional anticonvulsant medication for ongoing SE, 10 minutes after a single dose of SHP615 were reported.
Measured: 10 minutes post-dose
Percentage of Participants Who Failed to Respond to the Treatment With SHP615
Treatment failure/non-responder was defined as participants with continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline, for 10 mins or more after a single dose of the IP.
Measured: 10 minutes post-dose
Concentration of SHP615 in Plasma at 10 Minutes (C10)
Concentration of SHP615 in plasma at 10 minutes were reported.
Measured: 10 minutes post-dose
Maximum Plasma Concentration (Cmax) of SHP615
Cmax of SHP615 in plasma were reported.
Measured: 1, 3, 6 hours post-dose
Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma
AUC0-10 of SHP615 in plasma were reported. Here "min ng/mL" was minutes nanogram per milliliter.
Measured: Pre-dose, 10 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma
AUC0-60 of SHP615 in plasma were reported.
Measured: Pre-dose, 60 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma
AUC0-180 of SHP615 in plasma were reported.
Measured: Pre-dose, 180 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma
AUC(0-infinity) of SHP615 in plasma were reported.
Measured: Pre-dose, 1, 3, and 6 hours post-dose
Time at Maximum Concentration (Tmax) of SHP615 in Plasma
Tmax of SHP615 in plasma were reported.
Measured: 1, 3, and 6 hours post-dose
Elimination Half-life (T1/2) of SHP615 in Plasma
T1/2 of SHP615 in plasma were reported.
Measured: 1, 3, and 6 hours post-dose
Number of Participants With Respiratory Depression
Respiratory depression, included the following measures within 24 hours after administration of the IP: i) Persistent decrease in oxygen saturation to < 92 percent (%) measured at 10, 30 minutes, and 4, 6, and 24 hours post-dose (i.e, < 92 % on room air for 2 minutes or more after dosing while monitoring [per healthcare setting protocol and/or the clinical judgment of the physician]) ii) Increase in respiratory effort such that assisted ventilation is used (bag-valve-mask ventilation or endotracheal intubation). Number of participants with respiratory depression were reported.
Measured: From start of study drug administration up to follow-up (Day 8)
Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of IP. Number of participants with aspiration pneumonia identified as TEAEs were reported.
Measured: From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose
Sedation-Agitation was assessed, using the "Riker Sedation-Agitation Scale" (SAS) by the following 7-point scale: 7. dangerous agitation; 6. very agitated; 5. agitated; 4. calm, cooperative; 3. sedated; 2. very sedated; 1. unarousable. Change from baseline in riker sedation-agition scale at 24 hours post-dose were reported.
Measured: Baseline, 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of IP. Number of participants with TEAEs were reported.
Measured: From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose
Oxygen saturation at baseline was measured and recorded on room air. The investigator had recorded the oxygen saturation, oxygen delivery system and amount of oxygen administered during the study. Change from baseline in oxygen saturation percentage at 24 hours post-dose were reported.
Measured: Baseline, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start23 Oct 2017
- Primary completion19 Aug 2019
- Study completion19 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nervous System DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shire Study Physician, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03336645
- Sponsor's protocol ID
- SHP615-301
- Status last verified
- Jun 2020
- First submitted
- 6 Nov 2017
- Last updated
- 31 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Open-label Study to Determine the Efficacy, Safety, and Pharmacokinetics of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in the Hospital or Emergency Room
- ClinicalTrials.gov ID
- NCT03336645
- Acronym / sponsor ID
- SHP615-301
- Conditions
- Nervous System Diseases
- Keywords
- Seizure, Midazolam hydrochloride, Convulsive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 23 Oct 2017 (actual)
- Primary completion
- 19 Aug 2019 (actual)
- Study completion
- 19 Aug 2019 (actual)
- First posted
- 8 Nov 2017 (actual)
- Results
- Posted 31 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the efficacy, safety and pharmacokinetics of MHOS/SHP615 administered buccally in children with status epilepticus (convulsive) in a healthcare setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SHP615 | Experimental | Drug: SHP615Participants will receive a single age-specific dose (approximately 0.25 to 0.5 milligram per kilogram [mg/kg] as midazolam) of SHP615 oromucosal solution through buccal route upon onset of seizures. |
Who may qualify
- Ages
- 3 to 216 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Male and female participants whose corrected gestational age is greater than or equal to (>=) 52 weeks (gestational weeks plus the number of weeks after birth) and less than (<) 18 years (and weight greater than [>] 5 kilogram [kg]), at the time of investigational product administration. If the participant's exact age is not known, the participant should be excluded.
- Parent, guardian, or legally authorized representative (LAR) of the child provides informed consent (and assent, when applicable per Shire policy and country regulations) to participate in the study prior to participation in any protocol specific procedures. The participant may be prescreened by the investigator in their clinical practice and the parent, guardian, or LAR may sign informed consent before the participant presents to the healthcare setting for treatment of the seizure.
- Participant with generalized tonic-clonic SE with seizures accompanied by loss of consciousness with any of the following characteristics persistent at the time of study drug administration:
Key exclusion criteria (17 listed)
- Female participants who are pregnant, suspected to be pregnant, or nursing.
- Subjects with major trauma, not necessarily restricted to the head, as the cause of the seizure.
- Subjects with seizures due to illegal drug or acute alcoholic intoxication.
- Subjects with known or suspected recurrent seizures due to illegal drug or alcohol withdrawal.
- Subjects with history of seizures of psychogenic origin.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SHP615Also: Midazolam hydrochloride oromucosal solution, MHOSSHP615 oromucosal solution will be administered as a single age-specific dose (2.5, 5, 7.5 and 10 mg). | Drug | SHP615 |
Primary outcome
Percentage of Participants With Response Rate
Time frame: From start of study drug administration up to 30 minutes post-dose
Response rate was defined as the percentage of participants with therapeutic success. Therapeutic success was defined as the cessation of visible seizure activity within 10 minutes with a sustained absence of visible seizure activity for 30 minutes following a single dose of MHOS/SHP615 without the need for additional rescue medication.
18 secondary outcomes
Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours
Time frame: From start of study drug administration up to 1, 4 and 6 hours post-dose
Number of Participants With Time to Resolution of Seizures (Convulsions)
Time frame: From start of study drug administration up to follow-up (Day 8)
Number of Participants With Time to Recovery of Consciousness
Time frame: From start of study drug administration up to follow-up (Day 8)
Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)
Time frame: 10 minutes post-dose
Percentage of Participants Who Failed to Respond to the Treatment With SHP615
Time frame: 10 minutes post-dose
Concentration of SHP615 in Plasma at 10 Minutes (C10)
Time frame: 10 minutes post-dose
Maximum Plasma Concentration (Cmax) of SHP615
Time frame: 1, 3, 6 hours post-dose
Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma
Time frame: Pre-dose, 10 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma
Time frame: Pre-dose, 60 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma
Time frame: Pre-dose, 180 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma
Time frame: Pre-dose, 1, 3, and 6 hours post-dose
Time at Maximum Concentration (Tmax) of SHP615 in Plasma
Time frame: 1, 3, and 6 hours post-dose
Elimination Half-life (T1/2) of SHP615 in Plasma
Time frame: 1, 3, and 6 hours post-dose
Number of Participants With Respiratory Depression
Time frame: From start of study drug administration up to follow-up (Day 8)
Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose
Time frame: Baseline, 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose
Time frame: Baseline, 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shire Study Physician study director
Shire
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SHP615 in people with Nervous System Diseases, run by Shire at 23 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Response Rate (time frame: From start of study drug administration up to 30 minutes post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.