fenfluramine and Aura

fenfluramine has been researched along with Aura in 13 studies

Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.
fenfluramine : A secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reuptake pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertension.

Research

Studies (13)

Authors

Clinical Trials (4)

Trial Overview

Trial Outcomes

Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period

Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF. (NCT02926898)
Timeframe: 15 weeks (combined Titration + Maintenance Period)

Longest Convulsive Seizure-Free Interval (Days)

Comparison of the duration of the longest convulsive seizure-free interval (days) during the combined Titration + Maintenance Periods for the ZX008 0.5 mg/kg/day and placebo groups. (NCT02926898)
Timeframe: 15 weeks (combined Titration + Maintenance Period)

Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period

Percentage of participants who achieved ≥ a 50% reduction in convulsive seizure frequency from Baseline compared to the combined Titration + Maintenance Periods in the ZX008 0.5 mg/kg/day vs placebo groups. (NCT02926898)
Timeframe: 15 weeks (combined Titration + Maintenance Period)

Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period

Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies (ZX008-1501/ZX008-1502, and ZX008-1504 Cohort 2). Participants in 1504- Cohort 1 and de novo participants (who entered 1503 without having been in any of the core studies) did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Day 1 to EOS was divided by the total number of days from Day 1 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day convulsive seizure frequency (CSF). The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. (NCT02823145)
Timeframe: From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period

Baseline (Core) was defined as Baseline prior to double-blind treatment in the core studies. Participants in 1504-Cohort 1 and de novo participants did not have a Baseline (Core), and were not included in the analysis of this outcome measure. The total number of convulsive seizures from Month 2 to EOS was divided by the total number of days from Month 2 to EOS with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF. The change from Baseline for any individual participant was calculated by subtracting the Baseline (Core) from the post-baseline value. Monthly (28 day) CSF was based on electronic diary data obtained for each participant. (NCT02823145)
Timeframe: From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core)

Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period

Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion. (NCT02823145)
Timeframe: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period

Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment. (NCT02823145)
Timeframe: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period

A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported. (NCT02823145)
Timeframe: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)

Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period

Convulsive seizure frequency over time, reported as per 28 days was analyzed by the actual dose administered. Participants were grouped into low (0.2 to <0.4 mg/kg), medium (0.4 to <0.6 mg/kg), and high dose (>0.6 mg/kg) groups depending on their mean daily doses of ZX008 during the OLE Treatment period. For each participant, the seizure frequency per 28 days was calculated as the number of seizures recorded during the period, divided by the number of days in the period and multiplied by 28. The convulsive seizure frequency was calculated from all available data collected. (NCT02823145)
Timeframe: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)

Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36)

Monthly (28 day) CSF was based on electronic diary data obtained for each participant. The total number of convulsive seizures in the ith interval (CSF in OLE, where, i=1, 2, 3, … , 14 ) was divided by the total number of days in the ith interval with nonmissing diary data and the result was then multiplied by 28 to get a 28-day CSF of OLE. (NCT02823145)
Timeframe: At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36

Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period

Participants in the study were required to be on stable background therapy for the first 6 months of treatment, after which background AEDs could be reduced or withdrawn so long as one background AED remained. The percentage of participants who had changes in dose or type of concomitant AED medications during the first, second, third, fourth, fifth, and sixth months were analyzed and reported. (NCT02823145)
Timeframe: At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period

Area Under the Concentration Time Curve of ZX008 From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State

AUC0-24 is the area under the concentration time curve from time zero to 24 hours. (NCT02682927)
Timeframe: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Change From Baseline in Convulsive + Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo

Total seizure frequency were defined as the combination of convulsive and non-convulsive seizures. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The seizure frequency was based on electronic diary data obtained for each participant. The number of all seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day convulsive or non-convulsive seizure frequency. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Change From Baseline in Non-convulsive Seizure Frequency to the Combined Titration and Maintenance Period in Each ZX008 Treatment Arm Compared to Placebo

Non-convulsive seizures included focal without clear observable motor signs, absence or atypical absence, myoclonic and atonic. The number of non-convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day non-convulsive seizure frequency. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Change From Baseline in the Mean Convulsive Seizures Frequency (MCSF) to the Combined Titration and Maintenance Periods (T+M) in Participants Receiving ZX008 0.8 mg/kg/Day Compared to Placebo

Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Change From Baseline in the Mean Convulsive Seizures Frequency to the Combined Titration and Maintenance Period (T+M) in Participants Receiving ZX008 0.2 mg/kg/Day Compared to Placebo

Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Change From Baseline to Day 99 in the Overall Quality of Life Score From the Pediatric Quality of Life Inventory™ (PedsQL) Score in Each ZX008 Treatment Arm Compared to Placebo

The Pediatric Quality of Life Inventory (PedsQL) is a pediatric modular measure of health related quality of life (QoL) completed by the parent/caregiver on behalf of the participant. It consisted of 23 items across 4 core scales that measure physical (8 items), emotional, social, and school functioning (5 items each). Each of the responses to the 23 items is initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always). Scores are linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores correspond to better health-related QoL. The Overall Quality of Life is the average of all the items over the number of items answered on all the Scales. (NCT02682927)
Timeframe: From Baseline to Day 99

Change From Baseline to Day 99 in the Quality of Life in Childhood Epilepsy (QOLCE) Score to Measure Quality of Life in Each ZX008 Treatment Arm Compared to Placebo

QOLCE is a low-burden parent/caregiver completed assessment that evaluates how epilepsy affects day-to day functioning of the participant in various life areas, including physical activities, well being, cognition, social activities, behavior, and general health. QOLCE scores items on 16 subscales with possible 5-point response for each, where scores of 5 was best possible response and 1 was worst possible response. Item scores were then transformed to a 0-100 scale as follows: 1-0, 2-25, 3-50, 4-75, 5-100. A score for each participant for each subscale was calculated by averaging that participant's responses to each item in the subscale. Subscale scores per participant were averaged to obtain an overall QoL score for each participant. Higher the subscale and overall QoL scores, better the response. (NCT02682927)
Timeframe: From Baseline to Day 99

Change From Baseline to Day 99 in the Total Score From PedsQL Family Impact Module Score in Each ZX008 Treatment Arm Compared to Placebo

The PedsQL Family Impact measured the impact of pediatric chronic health conditions on parents and the family by measuring parent self-reported physical, emotional, social, and cognitive functioning, communication, worry, and family daily activities and relationships. There are a total of 36 items in the PedsQL: 6 items for Physical Functioning, 5 items each for Emotional Functioning, Cognitive Functioning and Worry, 4 for Social Functioning, 3 for Communication, 3 questions for Daily Activities, and 5 for Family Relationships. Each of the responses are initially scored on a 5-point Likert scale from 0 (Never) to 4 (Almost always) and then linearly transformed to a scale of 0 to 100, where 0=100, 1=75, 2=50, 3=25 and 4=0, and higher scores mean better health-related QoL. (NCT02682927)
Timeframe: From Baseline to Day 99

Elimination Half-life [t1/2 Beta] of ZX008 at Steady State

t1/2 beta is the elimination half-life. (NCT02682927)
Timeframe: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Longest Convulsive Seizure-free Interval in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period

The longest interval between convulsive seizures was calculated over the entire Titration and Maintenance Period and was derived as the maximum of the number of days between consecutive convulsive seizures. (NCT02682927)
Timeframe: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Maximum Observed Concentration of ZX008 Determined Directly From the Concentration Time Profile [Cmax] at Steady State

Cmax is the maximum observed concentration determined directly from the concentration-time profile. (NCT02682927)
Timeframe: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Number of Convulsive Seizure-free Days in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period

A convulsive seizure free day was defined as a day for which diary data are available and no convulsive seizures were reported. Convulsive seizure free days were taken from the electronic diary data. (NCT02682927)
Timeframe: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Percentage of Participants Who Achieved a ≥50% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period

Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 50% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Percentage of Participants Who Achieved a ≥75% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period

Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 75% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Percentage of Participants Who Achieved a 100% Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period

Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 100% reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Percentage of Participants Who Achieved Greater Than or Equal to 25% (≥25%) Reduction in Convulsive Seizure Frequency in Each ZX008 Treatment Arm Compared to Placebo From Baseline During the Titration and Maintenance Period

Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). A responder was a participant who experienced a 25% or greater reduction in convulsive seizure frequency per 28 days during Titration and Maintenance Period. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Percentage of Participants With Hospitalization and Healthcare Resource Utilization to Treat Seizures in Each ZX008 Treatment Arm Compared to Placebo During Study

Participants who utilized medical center care to treat a seizure during the study were reported. (NCT02682927)
Timeframe: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Percentage of Participants With Rescue Medication Usage in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period

Rescue medication was administered according to each participant's usual or prescribed regimen consisting of 1 or more medications. The usage of rescue medication (number of days and number of medications used per seizure episode) was based on electronic diary data obtained for each participant. The number of days rescue medication was taken (normalized to 28 days) was calculated for each participant. Multiple medications taken on the same day were counted once for that day. (NCT02682927)
Timeframe: From Baseline up to 14 weeks [Titration Period (2 weeks) plus Maintenance Period (12 weeks)]

Percentage of Participants With Status Epilepticus (SE) in Each ZX008 Treatment Arm Compared to Placebo During the Titration and Maintenance Period

The participants who either had SE episode recorded as an adverse event (AE) during treatment or a seizure greater than 10 minutes were reported for each treatment group. Additionally, a single participant who may had more than one episode of SE, and an episode of SE recorded as both an AE and as a seizure longer than 10 minutes was counted as a single event. (NCT02682927)
Timeframe: During 14 weeks Titration (2 weeks) and Maintenance Period (12 weeks) (average of 99 days)

Time to Maximum Concentration [Tmax] of ZX008 at Steady State

Tmax is the time to maximum concentration at steady state. (NCT02682927)
Timeframe: At Visit 8 (Day 43): pre-dose, 1, 2, and 4-6 hours postdose

Change From Baseline to Day 99 in Affective Symptoms of the Parent/Caregiver Using the Hospital Anxiety and Depression Scale (HADS) in Each ZX008 Treatment Arm Compared to Placebo

The HADS is a tool that was validated to assess presence of anxiety or depression in an outpatient non-psychiatric population. The HADS a 14-item scale that generates ordinal data for 2 dimensions: 1) Anxiety (7 items), and 2) Depression (7 items). Each item has 4 possible answers rated 0 to 3, of which 0 = No distress and 3 = worst distress. All answers to the items for a dimension with their respective rating are added resulting in a range for each dimension from 0-21, out of which of 0-7 = normal; 8-10=borderline abnormal; 11-21=abnormal. Scores for the entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress. (NCT02682927)
Timeframe: From Baseline to Day 99

Distribution of Duration of Convulsive Seizures (in Percentage) in Each ZX008 Treatment Arm Compared to Placebo at Baseline and During the Titration and Maintenance Period

Duration of single convulsive seizures during the Baseline and the duration over the Titration and Maintenance Period were reported by treatment group using categories as <2 minutes, 2 to 10 minutes and > 10 minutes as collected in the seizure diary. (NCT02682927)
Timeframe: At Baseline and 14 weeks of Titration (2 weeks) and Maintenance Period (12 weeks)

Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Rating Score, as Assessed by the Principal Investigator in Each ZX008 Treatment Arm Compared to Placebo

CGI-I scale measures improvement in the participant's clinical status from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The Principal Investigator rated their global impression of the participant's condition during the study. (NCT02682927)
Timeframe: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)

Percentage of Participants With Clinical Global Impression - Improvement Rating Score, as Assessed by the Parent/Caregiver in Each ZX008 Treatment Arm Compared to Placebo

CGI-I scale measures improvement in the participant's clinical status from Baseline. The severity of a participant's condition was rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), as follows: 1-very much improved,2-much improved, 3-minimally improved, 4- no change, 5-minimally worse, 6-much worse and 7-very much worse. The Parent/Caregiver rated their global impression of the participant's condition during the study. (NCT02682927)
Timeframe: At Visit 6 (Day 15), 8 (Day 43), 10 (Day 71) and 12 (Day 99)

Quality of Life (QoL) of the Parent/Caregiver Using the EQ- 5D-5L Scale in Each ZX008 Treatment Arm Compared to Placebo at Baseline and Day 99

"The EuroQOL-5 Dimensions-5 Levels scale produced by European QOL Group (EQ-5D-5L) health questionnaire is a health-related QOL instrument with 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5 dimensions of EQ-5D-5L health questionnaire were assessed on a Likert scale with 5 possible levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The categories slight problems, moderate problems, severe problems and extreme problems are collapsed into one response category problems. The QOL of the parent/caregiver was assessed and percentage of participants was reported for each item." (NCT02682927)
Timeframe: At Baseline and Day 99

Reviews

7 reviews available for fenfluramine and Aura

Trials

1 trial available for fenfluramine and Aura

Other Studies

5 other studies available for fenfluramine and Aura