E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10040785 |
E.1.2 | Term | Skin and subcutaneous tissue disorders |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of nalbuphine HCl ER tablets during a drug treatment period of up to 50 weeks. |
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E.2.2 | Secondary objectives of the trial |
•evaluate the safety of nalbuphine by achieved maintenance dose at the end of Treatment Week 4
•Assess skin lesion improvement using the metrics of the PAS
•Change from Baseline in Patient-Reported Outcome measures Worst and average itch NRS... (refers prot 4.2)
•Change between Baseline and final Treatment Period in PBI-P
•description of the percentage of patients utilizing various doses of nalbuphine HCl ER tablets by Study Week
•description of the frequency and reasons for dose up- and down-titration and treatment discontinuation
•Frequency and distribution by time on study of patients determined to meet failureto-improve criteria.
•Changes in the PRO measurements during the Washout Period after cessation of treatment of nalbuphine HCl ER tablets
•Time to first use of rescue medications and the number of days of use of rescue medications for itching
•evaluate the daily changes in the SOWS during the Washout Period after cessation of treatment of nalbuphine HCl ER tablets |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with prurigo nodularis who completed the TR03 study and have met Inclusion/Exclusion eligibility requirements for TR03ext:
1. Have been adequately informed of the nature and risks of the study and have given written informed consent at the conclusion of TR03 Visit 6 and prior to Visit 1a.
2. Have completed participation in the TR03 study.
Completion of participation in the TR03 study is defined as completion of Study Drug treatment through TR03 Visit 5 and completion of the TR03 Visit 6.
3. Agree to comply with the contraception requirements set by the protocol
4. Ability and acceptance to provide written informed consent.
5. Willing and able to comply with study requirements and restrictions
6. Agree to the confidential use and storage of all data (including photography) and use of all anonymized data for publication including scientific publication. |
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E.4 | Principal exclusion criteria |
1. Patients with a history of congestive heart failure of Class 2 or higher
as graded using the New York Heart Association scale (scale provided in
Appendix 5)
2. Patients with a history of angina pectoris grade 2 or higher as graded
using the Canadian Cardiovascular Society grading scale (scale provided
in Appendix 5)
3. History of ventricular tachycardia, torsade de pointes, family history
of sudden death, myocardial infarction or acute coronary syndrome
within the previous 3 months, as reported by the patient.
4. Serum potassium below the laboratory lower limit of normality at
TR03 visit 5. Note: Potassium levels below the laboratory lower limit of
normal at Visit 6 /Visit 1a should be repeated and potassium
supplementation provided as appropriate
5. QTcF interval >450ms on screening / Visit 1a EKG
6. Heart rate <50 BPM on any screening measurement. Patient with a
resting heart rate of <50 bpm will have it repeated once after 5 minutes
in the supine position, and if it remains <50 bpm during the repeat, they
will be considered a screen failure.
7. Use of a medication known to be associated with risk of torsade de
pointes (see Section 9.7.8, Safety Assessments, for hyperlink to the
CredibleMeds Filtered QTDrug List for cardiovascular related prohibited
medications with a known associated risk of Torsade de Pointes)
8. History of substance abuse within the past year as determined by the
Investigator
9. Significant medical condition or other factors that in the opinion of the
Investigator may interfere with the conduct of the study
10. Known hypersensitivity or allergy to nalbuphine or formulation
components
11. Is a pregnant or lactating female. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A description of the incidence and nature of TEAEs during Treatment Weeks 5-50 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
SECONDARY ENDPOINTS
Visit 1a or 1b will serve as the baseline visit for efficacy endpoints. Visit 1a will be the baseline for patients directly entering the Treatment Period as of Visit 1a. Visit 1b will be the baseline for patients entering the Treatment Period after participating in the Observation Period for any length of time.
• Assess skin lesion improvement using the metrics of the PAS
• Change from Baseline in Patient-Reported Outcome measures Worst itch NRS, average itch intensity NRS, VRS (itchy, burning and stinging), MOS Sleep-R, ItchyQoL, HADS) by Treatment Period study visit and Baseline NRS score
• Change between Baseline and the final Treatment Period visit in PBI-P
• A description of the percentage of patients utilizing various doses of nalbuphine HCl ER tablets by Study Week
• A description of the frequency and reasons for dose up- and down-titration and treatment discontinuation during the study
• Frequency and distribution by time on study of patients determined to meet failure-to-improve criteria
• Changes in the PRO measurements during the Washout Period after cessation of treatment of nalbuphine HCl ER tablets
• Time to first use of rescue medications and the number of days of use of rescue medications for itching
• To evaluate the daily changes in the Subjective Opiate Withdrawal Scale (SOWS) during the Washout Period after cessation of treatment of nalbuphine HCl ER tablets.
EXPLORATORY ENDPOINTS
The exploratory objectives of the study are to evaluate the effect of nalbuphine HCl ER tablets on:
• The potential of nalbuphine HCl ER tablets to impact on the measurement of nerve fiber density (histology) and MOR/KOR density (histology, Western Blot), as well as histological (H&E) changes in skin biopsies taken at Baseline and the final Treatment Period Visit when compared to biopsy material assessed during study TR03 (optional procedure at select sites only). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 | No |
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 |
Austria |
Germany |
Poland |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |