Narcolepsy
Conditions
Keywords
SUVN-G3031, Narcolepsy with and without cataplexy, Cataplexy, Narcolepsy Type 1, Narcolepsy Type 2, Excessive Daytime Sleepiness (EDS), Histamine H3 receptor, Samelisant
Brief summary
This study is of an investigational drug called SUVN-G3031 (Samelisant) as a possible treatment for narcolepsy with cataplexy or narcolepsy without cataplexy. The main purpose of this study is to learn how well the study drug works and how safe the study drug is compared to placebo.
Detailed description
This is a Phase 2, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SUVN-G3031 compared to placebo in participants with narcolepsy with and without cataplexy. Participants will be randomized at a ratio of 1:1:1 to 2 mg SUVN-G3031, 4 mg SUVN-G3031, or placebo. Each participant will receive study drug once daily, in a tablet formulation, for 14 days.
Interventions
DRUGSUVN-G3031
SUVN-G3031 Tablets
DRUGPlacebo
Placebo Tablets
Sponsors
Suven Life Sciences Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ages of 18 to 65 years (adult), inclusive. * Have narcolepsy with or without cataplexy (Na-1 or Na-2) based on the International Classification of Sleep Disorders (3rd edition) criteria (new or previously diagnosed). * Have undergone a multiple sleep latency test (MSLT) study showing an MSLT of ≤ 8 minutes. * An Epworth Sleepiness Scale (ESS) score of ≥ 12; and mean Maintenance of Wakefulness Test (MWT) time of \< 12 min. * Body mass index ranging from 18 to \< 45 kg/m2 * Negative urine drug screen. * A woman must be either not of childbearing potential or of childbearing potential practicing highly effective methods of birth control. * Willingness to complete the study protocol with full compliance with procedures and sign an informed consent form (ICF).
Exclusion criteria
* Habitual wake-up time after 8 AM as assessed by sleep diary, habitual sleep time of \< 6 hours, and habitual bedtime past 1 AM as determined by sleep diary entries. * Use of any investigational therapy within the 30-day period prior to enrollment. * Excessive caffeine (defined as \> 600 mg/per day) use at least 1 week prior to baseline assessments and during the course of the trial. * Nicotine dependence that has an effect on sleep (eg, a patient who routinely awakens at night to smoke). * Use of concurrent medications prescribed to treat narcolepsy as specified including stimulants, antidepressants and sodium oxybate. * Current diagnosis of or past treatment for syndromes known to cause sleep disruption or any other cause of daytime sleepiness. * Clinically significant ECG abnormalities. * An occupation requiring variable shift work, night shifts, or frequent overnight travel which disrupts sleep patterns.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale | Change from baseline in the mean total ESS score at Day 14 | The Epworth Sleepiness Scale (ESS) is a patient-reported questionnaire consisting of 8 questions. Each of the items are rated on a 4-point scale (0-3), based on the usual chances of dozing off or falling asleep while engaged in eight different activities. The total ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. Higher values represent a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Severity | Change from baseline in the mean CGI-S score at Day 14 | The Clinical Global Impressions of Severity (CGI-S) scale is used to rate the severity of the patient's illness by clinician, on a 7-point scale with score ranging from 1 - 7. Higher values represent a worse outcome. |
| Maintenance of Wakefulness Test | Change from baseline in the mean MWT score at Day 14 | Maintenance of Wakefulness Test (MWT) is an objective test of sleepiness that evaluates a person's ability to remain awake under soporific conditions for a defined period of time. In the MWT, time from start of the test to the time point of falling asleep will be measured, the total score can range from 0 - 30 minutes. Higher values represent a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change | Analysis of Patient Global Impression of Change (PGI-C) at Day 14 | The PGI-C is based on a 7-point scale, where at each time point the patient will rate the change from baseline using the following query: Since the start of the study, my overall status is: 1 = very much better; 2 = much better; 3 = a little better; 4 = no change; 5 = a little worse; 6 = much worse; 7 = very much worse. The PGI-C assessment will be based on change observed from baseline related to excessive daytime sleepiness rather than on the totality of the disease. |
| Clinical Global Impression of Change | Analysis of Clinical Global Impression of Change (CGI-C) at Day 14 | The CGI-C is based on a 7-point scale, where at each time point the physician will rate the change from baseline using the following query: Compared to the patient's condition at admission to the project \[prior to medication initiation\], this patient's condition is: 1 = very much improved since the initiation of treatment; 2 = much improved; 3 = minimally improved; 4 = no change from baseline (the initiation of treatment); 5 = minimally worse; 6 = much worse; 7 = very much worse since the initiation of treatment. The CGI-C assessment will be based on change observed from baseline related to excessive daytime sleepiness rather than on the totality of the disease. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SUVN-G3031 2mg Orally taken once daily for 14 days
SUVN-G3031: SUVN-G3031 Tablets | 63 |
| SUVN-G3031 4mg Orally taken once daily for 14 days
SUVN-G3031: SUVN-G3031 Tablets | 63 |
| Placebo Orally taken once daily for 14 days
Placebo: Placebo Tablets | 62 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 0 |
| Overall Study | Intercurrent Illness and Others | 3 | 5 | 6 |
| Overall Study | Physician Decision | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | SUVN-G3031 2mg | SUVN-G3031 4mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 29.8 years STANDARD_DEVIATION 8.59 | 34.0 years STANDARD_DEVIATION 10 | 33.6 years STANDARD_DEVIATION 10.02 | 32.5 years STANDARD_DEVIATION 9.7 |
| Clinical Global Impression of Severity (CGI-S) | 4.7 units on a scale STANDARD_DEVIATION 0.8 | 4.8 units on a scale STANDARD_DEVIATION 0.83 | 4.7 units on a scale STANDARD_DEVIATION 0.87 | 4.8 units on a scale STANDARD_DEVIATION 0.83 |
| Epworth Sleepiness Scale (ESS) | 17.3 units on a scale STANDARD_DEVIATION 2.76 | 17.5 units on a scale STANDARD_DEVIATION 2.84 | 17.1 units on a scale STANDARD_DEVIATION 3.03 | 17.3 units on a scale STANDARD_DEVIATION 2.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 11 Participants | 6 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 52 Participants | 56 Participants | 167 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Maintenance of Wakefulness Test (MWT) | 5.166 minutes STANDARD_DEVIATION 4.466 | 6.141 minutes STANDARD_DEVIATION 4.073 | 6.242 minutes STANDARD_DEVIATION 4.158 | 5.846 minutes STANDARD_DEVIATION 4.243 |
| Patient Global Impression of Change (PGI-C) | 4.8 units on a scale STANDARD_DEVIATION 1.08 | 4.7 units on a scale STANDARD_DEVIATION 1.03 | 4.8 units on a scale STANDARD_DEVIATION 1.01 | 4.8 units on a scale STANDARD_DEVIATION 1.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 16 Participants | 14 Participants | 43 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 47 Participants | 38 Participants | 43 Participants | 128 Participants |
| Region of Enrollment Canada | 6 participants | 3 participants | 4 participants | 13 participants |
| Region of Enrollment United States | 57 participants | 60 participants | 58 participants | 175 participants |
| Sex: Female, Male Female | 45 Participants | 44 Participants | 44 Participants | 133 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 18 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 0 / 63 | 0 / 62 |
| other Total, other adverse events | 17 / 63 | 34 / 63 | 5 / 62 |
| serious Total, serious adverse events | 0 / 63 | 0 / 63 | 0 / 62 |
Outcome results
Primary
Epworth Sleepiness Scale
The Epworth Sleepiness Scale (ESS) is a patient-reported questionnaire consisting of 8 questions. Each of the items are rated on a 4-point scale (0-3), based on the usual chances of dozing off or falling asleep while engaged in eight different activities. The total ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. Higher values represent a worse outcome.
Time frame: Change from baseline in the mean total ESS score at Day 14
Population: Intent to treat (ITT) population is considered for outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVN-G3031 2mg | Epworth Sleepiness Scale | -5.1 score on a scale | Standard Deviation 5 |
| SUVN-G3031 4mg | Epworth Sleepiness Scale | -5.6 score on a scale | Standard Deviation 5.46 |
| Placebo | Epworth Sleepiness Scale | -3.3 score on a scale | Standard Deviation 4.61 |
p-value: 0.024Mixed Models Analysis
Secondary
Clinical Global Impression of Severity
The Clinical Global Impressions of Severity (CGI-S) scale is used to rate the severity of the patient's illness by clinician, on a 7-point scale with score ranging from 1 - 7. Higher values represent a worse outcome.
Time frame: Change from baseline in the mean CGI-S score at Day 14
Population: Intent to treat (ITT) population is considered for outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVN-G3031 2mg | Clinical Global Impression of Severity | -1.2 score on a scale | Standard Deviation 1.24 |
| SUVN-G3031 4mg | Clinical Global Impression of Severity | -1.4 score on a scale | Standard Deviation 1.19 |
| Placebo | Clinical Global Impression of Severity | -0.8 score on a scale | Standard Deviation 1.17 |
p-value: 0.009Mixed Models Analysis
Secondary
Maintenance of Wakefulness Test
Maintenance of Wakefulness Test (MWT) is an objective test of sleepiness that evaluates a person's ability to remain awake under soporific conditions for a defined period of time. In the MWT, time from start of the test to the time point of falling asleep will be measured, the total score can range from 0 - 30 minutes. Higher values represent a better outcome.
Time frame: Change from baseline in the mean MWT score at Day 14
Population: Intent to treat (ITT) population is considered for outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVN-G3031 2mg | Maintenance of Wakefulness Test | 2.07 minutes | Standard Deviation 4.68 |
| SUVN-G3031 4mg | Maintenance of Wakefulness Test | 4.25 minutes | Standard Deviation 6.52 |
| Placebo | Maintenance of Wakefulness Test | 2.73 minutes | Standard Deviation 7 |
p-value: 0.734Mixed Models Analysis
Other Pre-specified
Clinical Global Impression of Change
The CGI-C is based on a 7-point scale, where at each time point the physician will rate the change from baseline using the following query: Compared to the patient's condition at admission to the project \[prior to medication initiation\], this patient's condition is: 1 = very much improved since the initiation of treatment; 2 = much improved; 3 = minimally improved; 4 = no change from baseline (the initiation of treatment); 5 = minimally worse; 6 = much worse; 7 = very much worse since the initiation of treatment. The CGI-C assessment will be based on change observed from baseline related to excessive daytime sleepiness rather than on the totality of the disease.
Time frame: Analysis of Clinical Global Impression of Change (CGI-C) at Day 14
Population: Intent to treat (ITT) population is considered for outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVN-G3031 2mg | Clinical Global Impression of Change | 2.8 score on a scale | Standard Deviation 1.01 |
| SUVN-G3031 4mg | Clinical Global Impression of Change | 2.6 score on a scale | Standard Deviation 0.92 |
| Placebo | Clinical Global Impression of Change | 3.5 score on a scale | Standard Deviation 0.91 |
p-value: <0.0001Mixed Models Analysis
Other Pre-specified
Patient Global Impression of Change
The PGI-C is based on a 7-point scale, where at each time point the patient will rate the change from baseline using the following query: Since the start of the study, my overall status is: 1 = very much better; 2 = much better; 3 = a little better; 4 = no change; 5 = a little worse; 6 = much worse; 7 = very much worse. The PGI-C assessment will be based on change observed from baseline related to excessive daytime sleepiness rather than on the totality of the disease.
Time frame: Analysis of Patient Global Impression of Change (PGI-C) at Day 14
Population: Intent to treat (ITT) population is considered for outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SUVN-G3031 2mg | Patient Global Impression of Change | 3.2 score on a scale | Standard Deviation 1.16 |
| SUVN-G3031 4mg | Patient Global Impression of Change | 2.8 score on a scale | Standard Deviation 1.1 |
| Placebo | Patient Global Impression of Change | 3.7 score on a scale | Standard Deviation 1.12 |
p-value: <0.001Mixed Models Analysis