E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016208 |
E.1.2 | Term | Familial periodic paralysis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether dichlorphenamide lowers the rate of attacks of weakness in HYP and HOP participants as measured by participant self-report over the last 8 weeks of a 9-week double blind period. |
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E.2.2 | Secondary objectives of the trial |
1. To test whether a larger percentage of placebo-treated HOP participants will reach the endpoint of acute worsening than of participants taking DCP. 2. To test whether the mean scores on composite strength measures, muscle mass, and from the physical health and mental health summary scales of the SF-36 will be significantly higher at the end of the 9-weeks in participants taking DCP than in participants taking placebo. 3. To test whether, after 12 months of open label treatment with DCP, HYP and HOP participants will have a positive mean change from baseline in composite strength measures and muscle mass during attack-free intervals.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for Hyperkalemic Periodic Paralysis (HYP): 1. Genetically definite, clinically definite or clinically probable HYP. 2. Male and female participants, age 18 and older who are able to comply with the study procedures. 3. Participants will be required to have distinct regular episodes of weakness by history with an average frequency of >1 /week and <3/day either on or off treatment, whichever is higher. 4. Normal TSH and T4. 5. Pregnancy: Women: non-childbearing potential (i.e., postmenopausal or surgically sterile) or must meet all of the following conditions: Use a medically accepted contraceptive regimen for at least 30 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug. Reliable forms of contraception include oral, implanted, or injected contraceptives; intrauterine devices in place for at least 3 months; or adequate barrier methods in conjunction with spermicide (abstinence is considered an acceptable contraceptive regimen). Women must be given a pregnancy test unless they are at least 2 years postmenopausal or surgically sterile.
Inclusion criteria for Hypokalemic Periodic Paralysis (HOP): 1. Genetically definite, clinically definite or clinically probable HOP. 2. Male and female participants, age 18 and older who are able to comply with the study procedures. 3. Participants will be required to have distinct regular episodes of weakness by history with an average frequency of >1 /week and <3/day either on or off treatment, whichever is higher. 4. Normal TSH and T4. 5. Pregnancy: Women: nonchildbearing potential (i.e., postmenopausal or surgically sterile) or must meet all of the following conditions: Use a medically accepted contraceptive regimen for at least 30 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug. Reliable forms of contraception include oral, implanted, or injected contraceptives; intrauterine devices in place for at least 3 months; or adequate barrier methods in conjunction with spermicide (abstinence is considered an acceptable contraceptive regimen). Women must be given a pregnancy test unless they are at least 2 years postmenopausal or surgically sterile.
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E.4 | Principal exclusion criteria |
Exclusion Criteria for Hyperkalemic Periodic Paralysis: None of the following can be present:
1. Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria) • Prolonged QT interval or complex ventricular ectopy between attacks • KIR 2.1 gene mutation • Distinctive physical features (2 out of 5) o Low set ears o Short stature o Hypo-/micro-gnathia o Clinodactyly o Hypo-/hypertelorism 2. Coincidental renal, hepatic, restrictive or obstructive lung disease, active thyroid, or heart disease 3. Chronic, non-congestive, angle-closure glaucoma 4. Use of any of the following medications for reasons other than treatment of periodic paralysis: diuretics, antiarrhythmics, corticosteroids, beta-blockers, calcium channel blockers, antiepileptics, magnesium 5. History of life-threatening episodes of respiratory muscle weakness or cardiac arrhythmias during attacks (prior to treatment) 6. History of worsening symptoms with the use of CAI’s 7. Any other neuromuscular disease
Exclusion criteria for Hypokalemic Periodic Paralysis: None of the following can be present:
1. Known mutation in the a subunit of sodium channel.
2. Evidence for Andersen-Tawil syndrome (any one of the following 3 criteria) • Prolonged QT interval or complex ventricular ectopy between attacks • Distinctive physical features (2 out of 5) o Low set ears o Short stature o Hypo-/micrognathia o Clinodactyly o Hypo-/hypertelorism • KIR 2.1 gene mutation
3. Coincidental renal, hepatic, active thyroid disease, restrictive or obstructive lung disease, or heart disease 4. Chronic, non-congestive, angle-closure glaucoma 5. Use of any of the following medications for reasons other than treatment of periodic paralysis: diuretics, antiarrhythmics, corticosteroids, beta-blockers, calcium channel blockers, antiepileptics, magnesium 6. History of life-threatening episodes of respiratory muscle weakness or cardiac arrhythmias during attacks (prior to treatment) 7. History of worsening symptoms with the use of CAI’s 8. Any other neuromuscular disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome variable of the initial 9-week comparisons of DCP, and placebo will be the number of attacks/week over the last 8 weeks. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |