Prader-Willi Syndrome
Conditions
Keywords
PWS, Prader-Willi Syndrome
Brief summary
The purpose of this is study is to evaluate the effects of DCCR (diazoxide choline controlled release tablets) in children and adults with Prader-Willi syndrome.
Interventions
DRUGDCCR
Once daily oral administration
DRUGPlacebo for DCCR
Once daily oral administration
Sponsors
Soleno Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide voluntary, written informed consent (parent(s) / legal guardian(s) of patient); provide voluntary, written assent (patients, as appropriate) * Genetically-confirmed Prader-Willi syndrome and hyperphagic * In a stable care setting for at least 6 months prior to Visit 1 * Caregiver must have been caring for the patient for at least 6 months prior to Visit 1
Exclusion criteria
* Have participated in an interventional clinical study (i.e., investigational drug or device, approved drugs or device evaluated for unapproved use) within prior 3 months * Positive urine pregnancy test (in females of child-bearing potential) or females who are pregnant or breastfeeding, and/or plan to become pregnant or to breast-feed during or within 30 days after study participation * Any other known disease and/or condition, which would prevent, in the opinion of the Investigator, the patient from completing all study visits and assessments required by the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) | Baseline to Visit 7 (Week 13) | Hyperphagia-related behaviors were assessed by the validated hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors that was completed by the caregiver. The HQ-CT consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36). The HQ-CT was assessed at Screening, Baseline (Visit 2), and approximately every 4 weeks post-dose at Week 4, Week 8, and Week 13. A decrease in score from baseline represented improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | at Visit 7 (Week 13) | The Clinical Global Impression of Improvement (CGI-I) is a single statement designed to assess the Investigator's overall perception of change in the subject's condition across the course of the clinical trial. The Investigator provided a response to Compared to the subject's condition at enrollment, the subject's condition is: by rating the subject's behavior using a 7-point response scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, and Very much worse. The Investigator only took into account the subject's PWS condition. |
| Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | at Visit 7 (Week 13) | The Caregiver Global Impression of Change (GI-C) is a single statement designed to assess the caregiver's overall perception of change in the subject across the course of the clinical trial. The caregiver provided a response to Please choose the response below that best describes the overall change in the person's PWS since they started taking the study medication using a 7-point graded response scale: Very much better, Moderately better, A little better, No change, A little worse, Moderately worse, and Very much worse. |
| Change in Fat Mass (kg) From Baseline at Visit 7 (Week 13) | Baseline to Visit 7 (Week 13) | Whole body scans were performed. Reports included a breakdown of the following regions: left arm, right arm, trunk, left leg, right leg, and head. Each region was evaluated for body fat mass (g). |
Countries
United Kingdom, United States
Participant flow
Recruitment details
People with Prader-Willi syndrome (PWS) were recruited for this study. Those who met the eligibility criteria were enrolled / randomized. Caregivers of subjects were responsible for completing the protocol-specified caregiver questionnaires and were not enrolled in this study. The first site in US started recruiting subjects on 17May2018; the first site in UK started recruiting subjects on 26Jun2019; all sites were either hospitals or academic medical centers.
Pre-assignment details
181 subjects were screened, 158 were eligible and entered the two-week, single-blind placebo run-in period and 127 subjects were enrolled / randomized in the trial. 126 of the 127 subjects took any amount of study drug.
Participants by arm
| Arm | Count |
|---|---|
| DCCR Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg DCCR tablets could be taken; DCCR was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed.
The target dose by weight (kg) was as follows:
Subjects weighing 20 to \< 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to \< 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to \< 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to \< 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to \< 135 took 450mg DCCR/day. Subjects randomized to the DCCR treatment group were titrated every 2 weeks until the target dose was achieved. | 84 |
| Placebo for DCCR Participants with PWS were dosed dependent on their weight; 25mg, 75mg or 150mg placebo for DCCR tablets could be taken; Placebo was taken daily. Tablets must be swallowed whole and should not be broken, crushed or chewed.
The target dose by weight (kg) was as follows:
Subjects weighing 20 to \< 30 kg took 100mg DCCR/day; Subjects weighing ≥ 30 to \< 40 took 150mg DCCR/day; Subjects weighing ≥ 40 to \< 65 took 225mg DCCR/day; Subjects weighing ≥ 65 to \< 100 took 375mg DCCR/day; Subjects weighing ≥ 100 to \< 135 took 450mg DCCR/day. Subjects randomized to the Placebo group were titrated on placebo, similar to the DCCR group. | 42 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Consent withdrawn by parent/legal guardian | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | DCCR | Placebo for DCCR | Total |
|---|---|---|---|
| Age, Continuous | 13.2 years | 13.6 years | 13.4 years |
| Age, Customized 12 to <18 years | 30 Participants | 11 Participants | 41 Participants |
| Age, Customized 18 to <65 years | 15 Participants | 10 Participants | 25 Participants |
| Age, Customized >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 8 to <12 years | 21 Participants | 14 Participants | 35 Participants |
| Age, Customized <8 years | 18 Participants | 7 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 7 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants | 34 Participants | 111 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| HQ-CT Total Score | 23.0 score on a scale STANDARD_DEVIATION 6.01 | 21.9 score on a scale STANDARD_DEVIATION 5.08 | 22.7 score on a scale STANDARD_DEVIATION 5.72 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Multiple | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 72 Participants | 34 Participants | 106 Participants |
| Sex: Female, Male Female | 47 Participants | 23 Participants | 70 Participants |
| Sex: Female, Male Male | 37 Participants | 19 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 42 |
| other Total, other adverse events | 69 / 84 | 31 / 42 |
| serious Total, serious adverse events | 6 / 84 | 0 / 42 |
Outcome results
Primary
Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13)
Hyperphagia-related behaviors were assessed by the validated hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors that was completed by the caregiver. The HQ-CT consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36). The HQ-CT was assessed at Screening, Baseline (Visit 2), and approximately every 4 weeks post-dose at Week 4, Week 8, and Week 13. A decrease in score from baseline represented improvement.
Time frame: Baseline to Visit 7 (Week 13)
Population: Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DCCR | Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) | -5.94 score on a scale | Standard Error 0.879 |
| Placebo for DCCR | Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) | -4.27 score on a scale | Standard Error 1.145 |
p-value: 0.198395% CI: [-4.24, 0.89]Mixed Models Analysis
Secondary
Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13)
The Caregiver Global Impression of Change (GI-C) is a single statement designed to assess the caregiver's overall perception of change in the subject across the course of the clinical trial. The caregiver provided a response to Please choose the response below that best describes the overall change in the person's PWS since they started taking the study medication using a 7-point graded response scale: Very much better, Moderately better, A little better, No change, A little worse, Moderately worse, and Very much worse.
Time frame: at Visit 7 (Week 13)
Population: Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 3 = Minimally improved | 22 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 5 = Minimally worse | 6 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 2 = Much improved | 6 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 6 = Much worse | 4 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 4 = No change | 39 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 7 = Very much worse | 1 Participants |
| DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 1 = Very Much Improved | 4 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 7 = Very much worse | 2 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 1 = Very Much Improved | 1 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 2 = Much improved | 3 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 3 = Minimally improved | 8 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 4 = No change | 20 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 5 = Minimally worse | 5 Participants |
| Placebo for DCCR | Caregiver Global Impression of Change (GI-C) at Visit 7 (Week 13) | 6 = Much worse | 3 Participants |
p-value: 0.4089Cochran-Mantel-Haenszel
Secondary
Change in Fat Mass (kg) From Baseline at Visit 7 (Week 13)
Whole body scans were performed. Reports included a breakdown of the following regions: left arm, right arm, trunk, left leg, right leg, and head. Each region was evaluated for body fat mass (g).
Time frame: Baseline to Visit 7 (Week 13)
Population: Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DCCR | Change in Fat Mass (kg) From Baseline at Visit 7 (Week 13) | -0.80 kg | Standard Error 0.356 |
| Placebo for DCCR | Change in Fat Mass (kg) From Baseline at Visit 7 (Week 13) | 0.25 kg | Standard Error 0.444 |
p-value: 0.022595% CI: [-1.95, -0.15]ANCOVA
Secondary
Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13)
The Clinical Global Impression of Improvement (CGI-I) is a single statement designed to assess the Investigator's overall perception of change in the subject's condition across the course of the clinical trial. The Investigator provided a response to Compared to the subject's condition at enrollment, the subject's condition is: by rating the subject's behavior using a 7-point response scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, and Very much worse. The Investigator only took into account the subject's PWS condition.
Time frame: at Visit 7 (Week 13)
Population: Intent to treat (ITT) population includes all randomized subjects who had a Baseline HQ-CT value and at least one post-Baseline HQ-CT value
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 3 = Minimally improved | 25 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 5 = Minimally worse | 11 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 2 = Much improved | 5 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 6 = Much worse | 0 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 4 = No change | 41 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 7 = Very much worse | 0 Participants |
| DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 1 = Very Much Improved | 0 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 7 = Very much worse | 0 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 1 = Very Much Improved | 0 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 2 = Much improved | 0 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 3 = Minimally improved | 2 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 4 = No change | 37 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 5 = Minimally worse | 3 Participants |
| Placebo for DCCR | Clinical Global Impression of Improvement (CGI-I) at Visit 7 (Week 13) | 6 = Much worse | 0 Participants |
p-value: 0.0294Cochran-Mantel-Haenszel
Post Hoc
Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) - Pre-COVID Analysis
Hyperphagia-related behaviors were assessed by the validated hyperphagia questionnaire for clinical trials (HQ-CT), an instrument designed to measure symptoms of food related preoccupations and behaviors that was completed by the caregiver. The HQ-CT consists of nine items with responses ranging from 0-4 units each (possible total score range: 0-36). The HQ-CT was assessed at Screening, Baseline (Visit 2), and approximately every 4 weeks post-dose at Week 4, Week 8, and Week 13. A decrease in score from baseline represented improvement.
Time frame: Baseline to Visit 7 (Week 13)
Population: The pre-COVID analysis population consisted of all subjects who had at least one post-baseline assessment of HQ-CT prior to March 1, 2020, when a national emergency was declared in the US as a result of the COVID-19 pandemic.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DCCR | Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) - Pre-COVID Analysis | -6.64 score on a scale | Standard Error 1.001 |
| Placebo for DCCR | Hyperphagia Questionnaire (HQ-CT) Change From Baseline at Visit 7 (Week 13) - Pre-COVID Analysis | -3.51 score on a scale | Standard Error 1.278 |
p-value: 0.036995% CI: [-6.06, -0.19]Mixed Models Analysis