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Diacomit
Sponsor
ARTGs
Device/Product name
Diacomit
Active Ingredient
Stiripentol
Date of decision
Published
Submission type
New chemical entity
ATC codes
N03AX17
Decision
Approved
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Diacomit was considered favourable for the therapeutic use approved.
What steps were involved in the decision process
Registration timeline
The following table summarises the key steps and dates for this application.
| Description | Date |
|---|---|
| Submission dossier accepted and first round evaluation commenced | 31 October 2016 |
| First round evaluation completed | 26 April 2017 |
| Sponsor provides responses on questions raised in first round evaluation | 27 May 2017 |
| Second round evaluation completed | 21 August 2017 |
| Delegate's overall benefit-risk assessment and request for Advisory Committee advice | 2 July 2019 |
| Sponsor's pre-Advisory Committee response | 16 July 2019 |
| Advisory Committee meeting | 1-2 August 2019 |
| Registration decision (Outcome) | 11 September 2019 |
| Completion of administrative activities and registration on ARTG | 13 September 2019 |
| Number of working days from submission dossier acceptance to registration decision* | 242 |
*Statutory timeframe for standard applications is 255 working days
Date of entry onto ARTG
Original publication date
Black triangle scheme
Yes. This product will remain in the scheme for 5 years, starting on the date the product is first supplied in Australia.
Dose forms
Capsule and Powder
Strength
250 mg and 500 mg
Other ingredients
In capsules: Povidone; Sodium starch glycolate type A; Magnesium stearate; Gelatin; Titanium dioxide; Erythrosine (Diacomit 250 mg only); Indigotin carmine (Diacomit 250 mg only).
In powder for oral suspension: Aspartame; Spray-dried glucose syrup; Povidone; Sodium starch glycolate type A; Erythrosine; Titanium dioxide; Carmellose sodium; Hyetellose; Arome Polv Tutti Frutti 25 H 245 flavour (PI: 111164).
Containers
Bottle and Sachet
Pack sizes
60
Routes of administration
Oral
Dosage
The dose of stiripentol is calculated on a mg/kg body weight basis. It is recommended to split the daily dose in two or three daily intakes (totalling the daily recommended dose per kg and per day). The initiation of adjunctive therapy with stiripentol should be undertaken gradually using upwards dose escalation to reach the recommended dose of 50 mg/kg/day.
Stiripentol dosage escalation should be gradual, starting with 20 mg/kg/day for 1 week, then 30 mg/kg/day for 1 week. Further dosage escalation is age dependent: - children less than 6 years should receive an additional 20 mg/kg/day in the third week, thus achieving the recommended dose of 50 mg/kg/day in three weeks; - children from 6 to less than 12 years should receive an additional 10 mg/kg/day each week, thus achieving the recommended dose of 50 mg/kg/day in four weeks; - children and adolescents 12 years and older should receive an additional 5 mg/kg/day each week until the optimum dose is reached based on clinical judgment.
For further information refer to the Product Information.
Pregnancy category
Category B3Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed.Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved
Diacomit (stiripentol) was approved for the following therapeutic use:
Diacomit is indicated for adjunctive treatment of generalised tonic-clonic and clonic seizures associated with severe myoclonic epilepsy in infancy (SMEI, also known as Dravet syndrome) in patients whose seizures are not adequately controlled with a benzodiazepine (usually clobazam) and valproate.
What is this medicine and how does it work
Stiripentol is an antiepileptic medicine intended for the treatment of severe myoclonic epilepsy in infancy (SMEI), also known as Dravet syndrome.The mechanism of antiepileptic activity of stiripentol is based on the potentiation of the gamma-Aminobutyric Acid (GABA)-ergic transmissions in the central nervous system (CNS). In vitro, stiripentol has been shown to directly enhance GABAA receptor-mediated transmission by acting both post-synaptically at a neuronal site coupled to the GABAA receptor and pre-synaptically to increase GABA release from nerve terminals. In rodent models, stiripentol appears to increase brain levels of GABA. This could occur by inhibition of synaptosomal uptake of GABA and/or inhibition of GABA transaminase. Stiripentol has been shown to enhance GABAA receptor-mediated transmission in the immature rat hippocampus and increase the mean open-duration (but not the open frequency) of GABAA receptor chloride channels.Stiripentol also potentiates the efficacy of clobazam and other anticonvulsants, as a result of the pharmacokinetic interactions.
What post-market commitments will the sponsor undertake
The following specific conditions of registration apply to this approval:
- The Diacomit EU-Risk Management Plan (RMP) (version 3.0, dated 9 June 2017, data lock point 18 August 2016), with Australian Specific Annex (version 0.1, dated October 2016), included with submission PM-2016-02336-1-1, to be revised to the satisfaction of the TGA, will be implemented in Australia.
Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs). Reports are to be provided in line with the current published list of EU reference dates and frequency of submission of PSURs until the period covered by such reports is not less than three years from the date of this approval letter. The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency's Guideline on good pharmacovigilance practices (GVP) Module VII-periodic safety update report (Rev1) Part VII.B Structures and processes. Not that submission of a PSUR does not constitute an application to vary the registration.
- Diacomit is to be included in the Black Triangle Scheme. The PI and CMI for Diacomit must include the black triangle symbol and mandatory accompanying text for five years, which starts from the date that the sponsor notifies the TGA of supply of the product.