Products
TGARO1H
Therapeutic Area(s): Insomnia 505(b)(2)
Phase of Development: Phase II
Development Status:
Phase II 505 (b)(2)
Product Description
TGAR01H is an intranasally administered hypnotic for the treatment
of insomnia. The active ingredient triazolam (Halcion® and
various generic preparations) is widely used as an orally administered
treatment for insomnia.
Treating insomnia with an oral formulation does not make a lot
of sense. The medication has to pass through the gastrointestinal
tract. It must be absorbed and pass through the enterohepatic
circulation that metabolizes most of it. Then the drug has to
pass through the blood stream to the brain. Meanwhile, the patient
who can’t sleep is waiting for something to happen.
FKP envisions a nasal spray sleeping medication which, when administered,
goes directly to the brain. The result is faster onset of sleep,
lower dose levels and fewer adverse events.
Lower doses of triazolam and greater control over the potential
for misuse and abuse are also envisioned.
The pre-IND document was sent to the FDA. The FDA agrees in principal
that TGAR01H should come under the 505(b)(2) regulation for the
following reasons:
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The application is
for a previously approved drug (triazolam) with a change in
the route of administration (oral to intranasal), relying
on the agency’s finding of safety and effectiveness
of the previously approved products. |
| • |
The data for the previously approved
products will be coupled with the additional data needed to
support the change from the approved products. |
| • |
The triazolam doses to be delivered
in TGAR01H will be designed to provide human exposures that
fall within or below the triazolam plasma concentrations and
AUC values that are approved as safe and effective. Therefore,
the additional data will consist of nonclinical and clinical
literature, as well as the appropriate safety and efficacy
studies using TGAR01H. |
Clinical Trials
Two clinical trials have been carried out on TGAR01H: a Phase
I pharmacokenitic trial using a cross over design comparing
TGAR01H at a 0.128 mg dose given intranasally with Halcion® 0.25
mg orally. Adverse events were similar between treatments.
After dose corrections, pharmacokenitic parameters obtained
after administration of 0.128 mg triazolam (1/2 of the oral
dose) via the prototype TGAR01H nasal spray formulation were
similar to those of a 0.25 mg Halcion® dose.
The second clinical trial was an EEG study in patients with insomnia.
A four period cross over design was employed comparing 0.25 mg
oral Halcion®, 0.0625 and 0.125 mg TGAR01H intranasally. All
night EEG recordings were made on the 3rd night of each treatment.
The 0.125 mg TGAR01H intranasal dose 1) significantly reduced
onset of sleep; 2) significantly increased total sleep time and
3) significantly increase stage II sleep compared to oral Halcion
0.25 mg or placebo.
Initially TGAR01H will be packaged in a one-time use individual
nasal device. A computer controlled (16 hour lock-out between
doses) multiple dose nasal device is under development.
Partners
Developmental and marketing partnerships are available.
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