Epilepsy
Conditions
Keywords
Cluster Seizures, Seizures, Clusters, Acute repetitive seizures
Brief summary
This study will assess long-term safety and tolerability of repeat dose diazepam nasal spray in adolescents and adults with cluster seizures, with a focus on potential local effects (changes in nasal mucosa, olfaction, and taste).
Interventions
Sponsors
Acorda Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of drug-resistant epilepsy * Patients who experience multiple episodes of acute repetitive seizures requiring at least one concomitant antiepileptic drug (AED) * Occurrence of at least 3 seizure clusters within the past 12 months, including at least one cluster in the 4 months prior to the Screening Visit * A caregiver must consent to participate together with the subject for purposes of observation and data collection * The caregiver must be present when the investigational product is administered * Screening body weight between 26 to 111 kg, inclusive
Exclusion criteria
* Female subject who is pregnant, breastfeeding, or planning to become pregnant * Presence or history of any abnormality or illness that may affect the absorption, distribution, metabolism or elimination of diazepam * Known allergy or hypersensitivity to diazepam, related drugs, or any of the formulation components * Positive screening test for ethanol or other drugs of abuse * Unable to receive medications intranasally
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening, weeks 12, 24, 36, 48 and 51 | The SIT is a 50-item multiple-choice standardized test of olfactory function. Scoring of the test in the ability to smell ranges from normal (Normosmia: score 35 - 40 Women; 34 - 40 Men); to inability to smell (Anosmia score 6 - 18); or Malingering (not engaged in the test) ranges 0 - 5. |
| Change From Baseline (Screening) in Nasal Mucosa. | Screening, Weeks 12, 24, 36, 48 and 51 | Change from baseline treatment visits using a focused nasal exam was based on a scale of nasal irritation none to Grade 4 septal perforation. |
| Change in Taste as Measured by a Taste Change Questionnaire | Weeks 12, 24 | Change in taste questionnaire was administered to subjects at every study visit only if the subject complained of a change in taste or as needed to report a related AE. The taste change profile included sweet, salty, sour, bitter, oily, sharp, chalky, metallic. The subject rated the change on a 10-point scale ranging from a weak change (1) to very strong (10). |
Countries
United States
Participant flow
Recruitment details
Adolescents or adults who have refractory epilepsy (drug resistant epilepsy per Kwan 2010) with a history of cluster seizures, also known as multiple episodes of acute repetitive seizures, for which acute treatment with a benzodiazepine was indicated as part of the standard of care or an individualized rescue treatment plan.
Participants by arm
| Arm | Count |
|---|---|
| Diazapam Nasal Spray (DZNS) Adults One dose of diazepam nasal spray is two intranasal sprays; one in each nostril using a nasal spray device. The dose is administered while the subject is sitting up or lying down. | 99 |
| Diazapam Nasal Spray (DZNS) Adolescents One dose of diazepam nasal spray is two intranasal sprays; one in each nostril using a nasal spray device. The dose is administered while the subject is sitting up or lying down. | 9 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Noncompliance with study drug | 0 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 9 |
| Overall Study | Withdrawn due to termination by Sponsor | 7 | 67 |
Baseline characteristics
| Characteristic | Diazapam Nasal Spray (DZNS) Adults | Diazapam Nasal Spray (DZNS) Adolescents | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 9 Participants | 16 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants | 0 Participants | 91 Participants |
| Age, Continuous | 34.6 years STANDARD_DEVIATION 12.58 | 13.4 years STANDARD_DEVIATION 1.13 | 32.9 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 7 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 75 Participants | 8 Participants | 83 Participants |
| Region of Enrollment United States | 99 Participants | 9 Participants | 108 Participants |
| Sex: Female, Male Female | 48 Participants | 3 Participants | 51 Participants |
| Sex: Female, Male Male | 51 Participants | 6 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 7 |
| other Total, other adverse events | 64 / 84 | 5 / 7 |
| serious Total, serious adverse events | 11 / 84 | 1 / 7 |
Outcome results
Primary
Change From Baseline (Screening) in Nasal Mucosa.
Change from baseline treatment visits using a focused nasal exam was based on a scale of nasal irritation none to Grade 4 septal perforation.
Time frame: Screening, Weeks 12, 24, 36, 48 and 51
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Erythema None | 20 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 1b | 3 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Discharge Mild | 14 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema None | 65 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Crusting of Mucosa None | 77 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 2 | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation None | 37 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation Grade 1a | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation Grade 1b | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Edema None | 35 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Bleeding/Epistaxis None | 39 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Crusting of Mucosa None | 37 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Discharge None | 12 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Discharge Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation None | 67 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 2 | 0 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Edema None | 71 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Edema Mild | 9 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Discharge None | 66 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema Mild | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema Moderate | 2 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Bleeding/Epistaxis None | 79 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Bleeding/Epistaxis Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Crusting of Mucosa Mild | 3 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation None | 50 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 1a | 5 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 1b | 3 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Edema None | 55 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Edema Mild | 4 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Discharge None | 49 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Discharge Mild | 10 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema None | 39 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema Mild | 20 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema Moderate | 0 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Bleeding/Epistaxis None | 58 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Bleeding/Epistaxis Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Crusting of Mucosa None | 58 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Crusting of Mucosa Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Edema Mild | 4 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Discharge None | 31 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Discharge Mild | 8 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Erythema None | 33 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Erythema Mild | 6 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Crusting of Mucosa Mild | 2 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Irritation None | 21 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Irritation Grade 1a | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Edema None | 21 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Edema Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Discharge None | 20 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Discharge Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 1a | 10 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Erythema Mild | 2 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Bleeding/Epistaxis None | 22 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Crusting of Mucosa None | 21 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Crusting of Mucosa Mild | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Irritation None | 12 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Irritation Grade 1a | 1 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Edema None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Discharge None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Erythema None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Bleeding/Epistaxis None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Crusting of Mucosa None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Irritation None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Edema None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Erythema None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Bleeding/Epistaxis None | 13 Participants |
| Diazepam Nasal Spray (Adults) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Crusting of Mucosa None | 13 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Erythema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 1a | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Bleeding/Epistaxis None | 4 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Erythema None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Discharge Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Bleeding/Epistaxis Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema None | 5 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Bleeding/Epistaxis Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Discharge None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 1b | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Crusting of Mucosa None | 4 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Crusting of Mucosa Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Erythema Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation Grade 1a | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Edema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Irritation Grade 1b | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Irritation None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Edema Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Bleeding/Epistaxis None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Bleeding/Epistaxis None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Edema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Discharge None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Discharge None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Erythema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Nasal Discharge Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Nasal Discharge Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation None | 6 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 1b | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Crusting of Mucosa None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Irritation Grade 2 | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Erythema None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Edema None | 6 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Crusting of Mucosa None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Edema Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Mucosal Erythema Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Nasal Discharge None | 6 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Crusting of Mucosa None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema Mild | 2 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Crusting of Mucosa Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Erythema Moderate | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 24: Crusting of Mucosa Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Mucosal Bleeding/Epistaxis None | 6 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Bleeding/Epistaxis None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Crusting of Mucosa None | 7 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Irritation None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Screening : Crusting of Mucosa Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Irritation None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation None | 4 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Irritation Grade 1a | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 1a | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 51: Mucosal Bleeding/Epistaxis None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Irritation Grade 2 | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Edema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Edema None | 3 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Nasal Irritation Grade 1a | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Edema Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Mucosal Edema Mild | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Discharge None | 4 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Crusting of Mucosa None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Nasal Discharge Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Discharge None | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema None | 4 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 48: Mucosal Edema None | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 36: Nasal Discharge Mild | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Change From Baseline (Screening) in Nasal Mucosa. | Week 12 : Mucosal Erythema Moderate | 0 Participants |
Primary
Change in Taste as Measured by a Taste Change Questionnaire
Change in taste questionnaire was administered to subjects at every study visit only if the subject complained of a change in taste or as needed to report a related AE. The taste change profile included sweet, salty, sour, bitter, oily, sharp, chalky, metallic. The subject rated the change on a 10-point scale ranging from a weak change (1) to very strong (10).
Time frame: Weeks 12, 24
Population: Safety Population - Number of subjects with at least one change in taste after dose administration. 6 Adults at 12 Weeks and 4 Adults at 24 weeks. No Adolescents participated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diazepam Nasal Spray (Adults) | Change in Taste as Measured by a Taste Change Questionnaire | Week 12 | 7.7 units on a scale | Standard Deviation 2.73 |
| Diazepam Nasal Spray (Adults) | Change in Taste as Measured by a Taste Change Questionnaire | Week 24 | 8.3 units on a scale | Standard Deviation 0.5 |
Primary
Olfactory Changes as Measured by the Smell Identification Test (SIT)
The SIT is a 50-item multiple-choice standardized test of olfactory function. Scoring of the test in the ability to smell ranges from normal (Normosmia: score 35 - 40 Women; 34 - 40 Men); to inability to smell (Anosmia score 6 - 18); or Malingering (not engaged in the test) ranges 0 - 5.
Time frame: Screening, weeks 12, 24, 36, 48 and 51
Population: Of 91 subjects in the Safety Population, data was available for 62 subjects at screening.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Normosmia | 18 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Mild Microsmia | 15 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Anosmia | 9 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Normosmia | 6 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Anosmia | 2 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Normosmia | 2 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Moderate Microsmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Anosmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Moderate Microsmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Severe Micromisia | 4 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Anosmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Moderate Microsmia | 8 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Severe Micromisia | 7 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Mild Microsmia | 16 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Moderate Microsmia | 9 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Severe Micromisia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Normosmia | 5 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Mild Microsmia | 9 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Moderate Microsmia | 2 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Severe Micromisia | 5 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Mild Microsmia | 6 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Moderate Microsmia | 4 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Severe Micromisia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Anosmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Mild Microsmia | 5 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Severe Micromisia | 3 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Normosmia | 1 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Mild Microsmia | 3 Participants |
| Diazepam Nasal Spray (Adults) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Moderate Microsmia | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Mild Microsmia | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Severe Micromisia | 1 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Severe Micromisia | 2 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Mild Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Severe Micromisia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Moderate Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Mild Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Normosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Mild Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Moderate Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Moderate Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Mild Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Severe Micromisia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Moderate Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Severe Micromisia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Severe Micromisia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 48 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Screening | Moderate Microsmia | 3 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 51 | Anosmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 24 | Probable Malingering | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 12 | Mild Microsmia | 0 Participants |
| Diazepam Nasal Spray (Adolescents) | Olfactory Changes as Measured by the Smell Identification Test (SIT) | Week 36 | Normosmia | 0 Participants |