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The purpose of this study is to evaluate the safety and effectiveness of intranasal FE 992097 in children and adults with Prader-Willi Syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Carbetocin (FE 992097) | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FE 992097 | Drug | Each spray pump actuation delivered a 50 μL volume of solution that contained 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril that delivered a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15) | The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items are classified into 3 domains; behavior, drive, and severity with each item rated on a five-point scale (1: not at all/none of the time/extremely easy to 5: extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Total score was the sum of all the items in the three domains and ranged from 11 (no hyperphagia behaviors) to 55 (most severe hyperphagia behaviors). Change from baseline in HPWSQ-R Total Score at Day 15 is presented for this outcome measure. | From Day 1 (baseline) to Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (Day 15) | The Clinical Global Impression (CGI) scale consists of a 7-point clinician rating of illness severity (1 = normal, not at all ill, 7 = among the most extremely ill patients), at the beginning of the trial (baseline) - Clinical Global Impression-Severity Rating (CGI-S) and a 7-point clinician rating of improvement of patient condition (1=very much improved since baseline/initiation of treatment, 7=very much worse from baseline), during and at the end of the trial (Day 15) - CGI-I. The CGI-I score at Day 15 is presented for this outcome measure. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Support | Ferring Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Florida University | Gainesville | Florida | United States | |||
| Winthrop University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29925684 | Derived | Dykens EM, Miller J, Angulo M, Roof E, Reidy M, Hatoum HT, Willey R, Bolton G, Korner P. Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome. JCI Insight. 2018 Jun 21;3(12):e98333. doi: 10.1172/jci.insight.98333. eCollection 2018 Jun 21. |
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In total, 38 subjects were screened and randomized. One subject in the Carbetocin (FE 992097) arm was randomized in error and did not receive the investigational medicinal product (IMP), and was listed as a screening failure. Of the randomized subjects, 37 subjects were exposed to IMP: 17 to Carbetocin (FE 992097) and 20 to placebo.
The trial was performed in the United States, and a total of 3 sites randomized subjects to the trial between Jan 2014 to Jul 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | Carbetocin (FE 992097) | Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| FG001 | Placebo | Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The analysis population included the safety analysis set (SAS) which consisted of all subjects who received any amount of the IMP. Analyses for the safety population were conducted according to the actual treatment received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Carbetocin (FE 992097) | Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Hyperphagia in Prader-Willi Syndrome (PWS) Questionnaires- Responsiveness (HPWSQ-R) Total Score at End-of-treatment (Day 15) | The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items are classified into 3 domains; behavior, drive, and severity with each item rated on a five-point scale (1: not at all/none of the time/extremely easy to 5: extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Total score was the sum of all the items in the three domains and ranged from 11 (no hyperphagia behaviors) to 55 (most severe hyperphagia behaviors). Change from baseline in HPWSQ-R Total Score at Day 15 is presented for this outcome measure. | The analysis population included the full analysis set (FAS) which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call [Day 8] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment. | Posted | Least Squares Mean | Standard Error | score on a scale | From Day 1 (baseline) to Day 15 |
The adverse events (AEs) were recorded from signing of the informed consent until the Day 19 follow-up phone call.
Adverse events that began during the Treatment Period (period during which a subject received IMP) or worsening of a pre-existing medical condition (treatment-emergent AEs) are presented for the SAS.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Carbetocin (FE 992097) | Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | +1 862-286-5200 | Disclosure@ferring.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 24, 2014 | Aug 27, 2024 | Prot_SAP_000.pdf |
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|
| Placebo | Drug | Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
|
| At Day 15 |
| Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15) | The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items were classified into 3 domains; behavior, drive, and severity with each item rated on a five-point score range from 1 (not at all/none of the time/extremely easy) to 5 (extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Changes in the HPWSQ-R Total Score and in the Domain Scores (behavior, drive, and severity) at Day 15 is presented for this outcome measure. HPWSQ-R Behavior, Drive and Severity scores range from 5-25, 4-20, and 2-10, respectively, with higher scores indicating a worse outcome. Change from baseline is presented = (Day 15 score minus Baseline score). | From Day 1 (baseline) to Day 15 |
| Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (Day 15) | The CY-BOCS is a clinician rated, semi-structured inventory of specific symptoms and symptom severity in pediatric obsessive-compulsive disorder (OCD). Total scores on the CY-BOCS are calculated using a symptom checklist and severity scale. The 10 severity items are summed to produce an Obsessions Severity Score (5 items), Compulsions Severity Score (5 items), and Total score (sum of all 10 severity items). The total score is calculated by summing the 10 individual scores and ranges from 0 (no obsessions or compulsions) to 40 (most severe OC). | From Day 1 (baseline) to Day 15 |
| Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (Day 15) | The Food Domain Score of the Reiss Profile consisted of 7 questions that pertain to food seeking behavior. The questions were rated on a five point scale ranging from -2 (strongly disagree; this phrase is not at all characteristic of the person) to 2 (strongly agree; this phrase is definitely characteristic of the person). Total score was defined as the sum of all individual item scores. The total score ranged from -14 to 14 with higher scores indicating higher severity. Change from baseline in Food Domain of the Reiss Profile at Day 15 is presented for this outcome measure. | From Day 1 (baseline) to Day 15 |
| Mineola |
| New York |
| United States |
| Vanderbilt University | Nashville | Tennessee | United States |
| BG001 |
| Placebo |
Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Baseline Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| ID | Title | Description |
|---|
| OG000 | Carbetocin (FE 992097) | Each spray pump actuation delivered a 50 μL volume of solution containing 1.6 mg carbetocin (FE 992097); each dose consisted of 3 spray pump actuations in each nostril delivering a total of 9.6 mg carbetocin. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
| OG001 | Placebo | Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. |
|
|
|
| Secondary | Clinical Global Impression- Improvement After Treatment (CGI-I) Score at End-of-treatment (Day 15) | The Clinical Global Impression (CGI) scale consists of a 7-point clinician rating of illness severity (1 = normal, not at all ill, 7 = among the most extremely ill patients), at the beginning of the trial (baseline) - Clinical Global Impression-Severity Rating (CGI-S) and a 7-point clinician rating of improvement of patient condition (1=very much improved since baseline/initiation of treatment, 7=very much worse from baseline), during and at the end of the trial (Day 15) - CGI-I. The CGI-I score at Day 15 is presented for this outcome measure. | The analysis population included the full analysis set (FAS) which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call [Day 8] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment. Number of subjects analyzed signifies those subjects who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | score on a scale | At Day 15 |
|
|
|
|
| Secondary | Change From Baseline in HPWSQ-R Domain Scores (Behavior, Drive and Severity) at End-of-treatment (Day 15) | The HPWSQ-R is an 11-item questionnaire examining the psychological, developmental, and neurobiological correlates of hyperphagia in PWS. The items were classified into 3 domains; behavior, drive, and severity with each item rated on a five-point score range from 1 (not at all/none of the time/extremely easy) to 5 (extremely/all of the time/extremely hard). The questionnaire was completed by the parent/caregiver using a 1-week recall period. Changes in the HPWSQ-R Total Score and in the Domain Scores (behavior, drive, and severity) at Day 15 is presented for this outcome measure. HPWSQ-R Behavior, Drive and Severity scores range from 5-25, 4-20, and 2-10, respectively, with higher scores indicating a worse outcome. Change from baseline is presented = (Day 15 score minus Baseline score). | The analysis population included the FAS which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call [Day 8] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment. | Posted | Least Squares Mean | Full Range | score on a scale | From Day 1 (baseline) to Day 15 |
|
|
|
|
| Secondary | Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale Score (CY-BOCS) at End-of-treatment (Day 15) | The CY-BOCS is a clinician rated, semi-structured inventory of specific symptoms and symptom severity in pediatric obsessive-compulsive disorder (OCD). Total scores on the CY-BOCS are calculated using a symptom checklist and severity scale. The 10 severity items are summed to produce an Obsessions Severity Score (5 items), Compulsions Severity Score (5 items), and Total score (sum of all 10 severity items). The total score is calculated by summing the 10 individual scores and ranges from 0 (no obsessions or compulsions) to 40 (most severe OC). | The analysis population included the FAS which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call [Day 8] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment. Number of subjects analyzed signifies those subjects who were evaluable for this endpoint | Posted | Least Squares Mean | Standard Error | score on a scale | From Day 1 (baseline) to Day 15 |
|
|
|
|
| Secondary | Change From Baseline in the Food Domain Score of the Reiss Profile at End-of-treatment (Day 15) | The Food Domain Score of the Reiss Profile consisted of 7 questions that pertain to food seeking behavior. The questions were rated on a five point scale ranging from -2 (strongly disagree; this phrase is not at all characteristic of the person) to 2 (strongly agree; this phrase is definitely characteristic of the person). Total score was defined as the sum of all individual item scores. The total score ranged from -14 to 14 with higher scores indicating higher severity. Change from baseline in Food Domain of the Reiss Profile at Day 15 is presented for this outcome measure. | The analysis population included the FAS which consisted of all subjects in the safety population who had the primary efficacy endpoint measured (at baseline and phone call [Day 8] ±1 or Day 15). Analyses for the FAS were conducted according to the randomized treatment. Number of subjects analyzed signifies those subjects who were evaluable for this endpoint. | Posted | Least Squares Mean | Standard Error | score on a scale | From Day 1 (baseline) to Day 15 |
|
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 7 |
| 17 |
| EG001 | Placebo | Each spray pump actuation delivered a 50 μL volume of sterile sodium chloride solution 0.9%; each dose consisted of 3 spray pump actuations in each nostril. Parents were instructed to administer 3 intranasal spray actuations in each nostril 3 times daily before meals for 14 days. | 0 | 20 | 0 | 20 | 8 | 20 |
| Diarrhea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Conjunctivitis infective | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Medication error | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Urine analysis abnormal | Investigations | MedDRA (16.1) | Systematic Assessment |
|
| Hyperphagia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Aggression | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sleep Disorder | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
| Severity |
|
HPWSQ-R Domain score: Drive
| ANCOVA |
Treatment groups were compared using ANCOVA model with treatment and site as fixed effects and HPWSQ-R domain score -at baseline as a covariate. |
| 0.1436 |
| LS Mean Difference |
| -1.6 |
| 1-Sided |
| 90 |
| 0.3 |
| Other |
| HPWSQ-R Domain score: Severity | ANCOVA | Treatment groups were compared using ANCOVA model with treatment and site as fixed effects and HPWSQ-R domain score -at baseline as a covariate. | 0.0248 | LS Mean Difference | -1.5 | 1-Sided | 90 | -0.5 | Other |