Download PDF

Clinical Trial Results:
An Open Label Extension Study of the Safety and Anti-Pruritic Efficacy of Nalbuphine HCL ER Tablets in Prurigo Nodularis Patients.

Summary
EudraCT number	2013-005628-41
Trial protocol	DE PL AT
Global end of trial date	26 Jul 2017

Results information
Results version number	v1(current)
This version publication date	29 Apr 2018
First version publication date	29 Apr 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

TR03ext

ISRCTN number

US NCT number

NCT02174432

WHO universal trial number (UTN)

Sponsor organisation name

Trevi Therapeutics, Inc

Sponsor organisation address

195 Church Street, 14th Floor, New Haven, United States, CT 06510 USA

Public contact

Clinical Trial Information, Trevi Therapeutics, Inc., +1 203304-2499, Thomas.Sciascia@trevitherapeutics.com

Scientific contact

Clinical Trial Information, Trevi Therapeutics, Inc., +1 203304-2499, Thomas.Sciascia@trevitherapeutics.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 May 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 May 2017

Global end of trial reached?

Yes

Global end of trial date

26 Jul 2017

Was the trial ended prematurely?

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.

Protection of trial subjects

The first dosing day was on either Visit 1a or Visit 1b. Titration was based on tolerability. If the subject was experiencing a study drug-related AE or an AE that may have been aggravated by study drug up-titration, the study drug dose was not increased, regardless of the NRS score. Any subject whose condition significantly changed after entering the study was carefully evaluated by the investigator and discussed with the medical monitor. Such subjects were to have been withdrawn from the study if continuing in the study would have placed them at risk or would have compromised the results of the study. Subjects who prematurely discontinued from the study were asked to undergo and complete early termination visit procedures and evaluations that may have been necessary to ensure that the subject was free of untoward effects and were asked to seek appropriate follow-up for any continuing problems. This single-arm, open-label study provides descriptive data on a modest cohort of subjects with PN that is unique for the prolonged duration of observed therapy.

Background therapy

There is no approved therapy for Prurigo Nodularis (PN) related pruritus in the United States or Europe. If Nalbuphine proves to be effective, PN patients could potentially benefit from this approach to treatment. Patients were allowed to receive all clinically indicated medications during the study with the exceptions noted in the study protocol. Rescue Anti-Pruritic Medications: Concomitant use of medications for pruritus (including prior medications that are ongoing and remain at the same dose and dosing frequency following randomization) was not prohibited except as described in the protocol.

Evidence for comparator

This extension study was open-label and the subjects were not randomly assigned to a particular study treatment. They continued receiving the same study treatment to which they have been randomly assigned for.

Actual start date of recruitment

24 Aug 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 9

Country: Number of subjects enrolled

Austria: 7

Country: Number of subjects enrolled

Germany: 20

Country: Number of subjects enrolled

United States: 5

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Eligible subjects were subjects who had successfully completed the TR03 study. A total of forty-one subjects were enrolled in the study. Thirty-six (87.8%) subjects were treated and of these, 16 (44.4%) subjects completed the study.

Screening details

Subjects either entered directly into the drug treatment period (worst itch NRS ≥5) or entered an 12-weeks extended screening period of a no-drug treatment observation period (worst itch NRS <5) based on their reported NRS scores on the first visit (Visit 1a).

Number of subjects started

Number of subjects completed

Reason: Number of subjects

screen failure: 5

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Nalbuphine 90mg BID target dose

Arm description

Nalbuphine HCl ER tablets: 90 mg target dose. Subjects enrolled into TR03 extension and received drug as early as approximately 2 weeks following their last dose of study drug in the parent TR03 study. TR03 core study patients who provided consent to participate in the TR03 extension study by the TR03 core study treatment to which they were randomized. Subjects were only dispensed a single strength of the study drug (e.g., either 30-mg bottles or 60-mg bottles at a visit). Completion is defined as completing study drug treatment through the End of Treatment Visit (TV14) during the TR03 extension study even if there were intervening missed doses.

Arm type

Experimental

Investigational medicinal product name

Nalbuphine HCl ER

Investigational medicinal product code

Other name

(NAL ER)

Pharmaceutical forms

Modified-release tablet

Routes of administration

Oral use

Dosage and administration details

Subjects were titrated to tolerability beginning with a 30-mg dose on Day 1 (Visit 1a or Visit 1b) with a dose increase of 30 mg BID not more often than every 3 to 4 days in order to attain steady-state plasma concentrations of Nalbuphine at each dose. Subjects were instructed to up-titrate beginning with a single 30-mg dose in the evening and then to begin dosing with an increased 30 mg BID dose the following day. Dose titrations were maintained for 3 to 4 days before further up-titration of the subject’s dose was attempted. If the tolerance level became unacceptable to either the subject or the investigator, the dose was reduced incrementally until tolerance was stabilized (dose reduction by 30 mg BID if subject was at the 30-mg, 60-mg, 90-mg, or 120-mg dose level and dose reduction by 60 mg BID if subject was at the 180-mg dose level). Subjects who did not tolerate the 180-mg BID dose level were down-titrated to the 120-mg BID dose level and maintained at that level when stabilized.

Nalbuphine 180 mg BID target dose

Arm description

Nalbuphine HCl ER tablets: 180 mg target dose. Subjects enrolled into TR03 extension and received drug as early as approximately 2 weeks following their last dose of study drug in the parent TR03 study. TR03 core study patients who provided consent to participate in the TR03 extension study by the TR03 core study treatment to which they were randomized. Subjects were only dispensed a single strength of the study drug (e.g., either 30-mg bottles or 60-mg bottles at a visit). Completion is defined as completing study drug treatment through the End of Treatment Visit (TV14) during the TR03 extension study even if there were intervening missed doses.

Arm type

Experimental

Investigational medicinal product name

Nalbuphine HCl ER

Investigational medicinal product code

Other name

(NAL ER)

Pharmaceutical forms

Modified-release tablet

Routes of administration

Oral use

Dosage and administration details

Placebo

Arm description

Subjects enrolled into TR03 extension and received drug as early as approximately 2 weeks following their last dose of study drug in the parent TR03 study. TR03 core study patients who provided consent to participate in the TR03 extension study by the TR03 core study treatment to which they were randomized. Completion is defined as completing study drug treatment through the End of Treatment Visit (TV14) during the TR03 extension study even if there were intervening missed doses.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Approximately one-third of subjects were expected to enter the study after having received placebo in the TR03 study.

Number of subjects in period 1 ^[1]	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo
Started	16	8	12
Completed	8	5	3
Not completed	8	3	9
Failure to improve criterion met	2	-	-
Physician decision	-	-	1
Adverse event, non-fatal	2	-	3
other	-	3	3
Lack of efficacy	4	-	2

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: For up to 12 extended screening weeks, subjects in the no-drug treatment observation period were allowed to transition into the drug treatment period if their worst itch NRS increased to ≥5. After 12 extended screening weeks, subjects who were not eligible for the treatment period were considered a screen failure from the study and did not enter in the baseline for study drug administration.

Baseline characteristics

Top of page

Reporting group title

Nalbuphine 90mg BID target dose

Reporting group description

Reporting group title

Nalbuphine 180 mg BID target dose

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Total
Number of subjects	16	8	12	36
Age categorical
Units: Subjects
Adults (18-64 years)	15	6	11	32
From 65-84 years	1	2	1	4
Age continuous
Overall, the median age was 56.5 years and ranged from 23 to 75 years.
Units: years
median (full range (min-max))	55.5 (32 to 69)	50.5 (24 to 69)	56.4 (23 to 75)	-
Gender categorical
Units: Subjects
Female	8	2	6	16
Male	8	6	6	20

Subject analysis set title

Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

A total of 41 (100%) subjects were included in the all enrolled population and 36 (87.8%) subjects were included in the safety population. Safety population consisted of all enrolled subjects who received a single dose of study drug in the TR03 extension study. The safety population was used to evaluate the safety and efficacy endpoints defined for this study.

Subject analysis sets values	Safety population
Number of subjects	36
Age categorical
Units: Subjects
Adults (18-64 years)	32
From 65-84 years	4
Age continuous
Overall, the median age was 56.5 years and ranged from 23 to 75 years.
Units: years
median (full range (min-max))	56.5 (23 to 75)
Gender categorical
Units: Subjects
Female	16
Male	20

End points

Top of page

Reporting group title

Nalbuphine 90mg BID target dose

Reporting group description

Reporting group title

Nalbuphine 180 mg BID target dose

Reporting group description

Reporting group title

Placebo

Reporting group description

Subject analysis set title

Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50

Top of page

End point title

A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50 ^[1]

End point description

End point type

Primary

End point timeframe

Visit 1a was the baseline for subjects directly entering the treatment period as of Visit 1a and Visit 1b was the baseline for subjects entering the treatment period after participating for up to 50 weeks.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As this was a safety extension study for which subjects were recruited from subjects who had completed parent Study TR03, the sample size could not be predicted. No formal sample size calculations were performed and no inferential statistics were planned. No formal statistical analysis was performed on safety outcomes; inferences, if any, were derived through clinical review and interpretation.

End point values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Safety population
Number of subjects analysed	16	8	12	36
Units: number of subjects
TEAEs with maximum severity of Grade 1	3	2	3	8
TEAEs with maximum severity of Grade 2	9	4	6	19
TEAEs with maximum severity of Grade 3	2	2	2	6
TEAEs with maximum severity of Grade 4	1	0	0	1
TEAEs with maximum severuty of Grade 5	0	0	0	0

No statistical analyses for this end point

Primary: Treatment-Emergent Adverse Events of Special Interest

Top of page

End point title

Treatment-Emergent Adverse Events of Special Interest ^[2]

End point description

Treatment-Emergent Adverse Events of Special Interest Time to onset of event was defined as: (earliest event onset date – the date of first dose of study drug + 1). For subjects who did not experience an event, time to onset was censored at the date of their last study visit. Duration of event was defined as: (event resolution date – event onset date + 1). For subjects with an event that remained ongoing at the time of study discontinuation, event duration was censored at the date of their last study visit. For some treatment administrations, time to onset of first event (days) and duration of first event (days) were not not calculable.

End point type

Primary

End point timeframe

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As this was a safety extension study for which subjects were recruited from subjects who had completed parent Study TR03, the sample size could not be predicted. No formal sample size calculations were performed and no inferential statistics were planned. No formal statistical analysis was performed on safety outcomes; inferences, if any, were derived through clinical review and interpretation.

End point values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Safety population
Number of subjects analysed	16	8	12	36
Units: number of subjects experienced the TEAE
Nausea	2	1	6	9
Vomiting	0	0	1	1
Constipation	2	1	2	5
Somnolence	1	0	3	4
Sedation	0	0	0	0
Dizziness	4	2	2	8
Vertigo	1	0	5	6

No statistical analyses for this end point

Secondary: Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

Top of page

End point title

Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

End point description

Change from baseline: post-baseline value – baseline value. For the change from baseline, only subjects with a value at both baseline visit and the specific post-baseline week were included. Numerical Rating Scale (NRS) score ranges from 0 (no itching) to 10 (worst possible Itching). Baseline was defined as the worst itch intensity NRS score at Visit 1a or 1b prior to treatment with study drug. Last observed post-baseline value was defined as the worst itch intensity NRS score at the last post-baseline visit, up to and including the washout and safety follow-up period visit. Only subjects with a value at both baseline visit and a post-baseline visit were included. All efficacy endpoints were evaluated through the generation of descriptive summary statistics.

End point type

Secondary

End point timeframe

From week 5 to up to 50 weeks, followed by 2-week washout for a total of 53 weeks.

End point values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Safety population
Number of subjects analysed	16 ^[3]	6 ^[4]	12 ^[5]	34 ^[6]
Units: Mean change from baseline
arithmetic mean (standard deviation)
Visit 3/Week 5	-2.4 ± 2.3	-1 ± 1.7	-1.8 ± 2.2	-2 ± 2.2

Notes
[3] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[4] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[5] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[6] - Only patients with a value at both baseline visit and a post-baseline visit are included.

No statistical analyses for this end point

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

Top of page

End point title

Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

End point description

End point type

Secondary

End point timeframe

From week 5 to up to 50 weeks, followed by 2-week washout for a total of 53 weeks.

End point values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Safety population
Number of subjects analysed	8 ^[7]	5 ^[8]	3 ^[9]	16 ^[10]
Units: Mean change from baseline
arithmetic mean (standard deviation)
VISIT 14/EOT	-4.6 ± 1.4	-4.2 ± 1.1	-3 ± 1.0	-4.2 ± 1.3

Notes
[7] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[8] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[9] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[10] - Only patients with a value at both baseline visit and a post-baseline visit are included.

No statistical analyses for this end point

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

Top of page

End point title

Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

End point description

End point type

Secondary

End point timeframe

From week 5 to up to 50 weeks, followed by 2-week washout for a total of 53 weeks.

End point values	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo	Safety population
Number of subjects analysed	8 ^[11]	5	3 ^[12]	15 ^[13]
Units: Mean change from baseline
arithmetic mean (standard deviation)
VISIT 15/WASHOUT FU	-3.3 ± 1.7	-4.3 ± 1.9	-3 ± 1.7	-3.5 ± 1.7

Notes
[11] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[12] - Only patients with a value at both baseline visit and a post-baseline visit are included.
[13] - Only patients with a value at both baseline visit and a post-baseline visit are included.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were assigned to a study period based on the planned study visit dates, where the planned visit date for Visit 1a/1b is the date of first dose of study drug.

Adverse event reporting additional description

The total number of serious adverse events (SAEs) counts all treatment-emergent SAEs for subjects. At each level of subject summarization, a subject was counted once if the subject reported 1 or more events.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Nalbuphine 90mg BID target dose

Reporting group description

Reporting group title

Nalbuphine 180 mg BID target dose

Reporting group description

Reporting group title

Placebo

Reporting group description

Serious adverse events	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 16 (6.25%)	0 / 8 (0.00%)	1 / 12 (8.33%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Injury, poisoning and procedural complications
Joint injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 16 (6.25%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Tenosynovitis stenosans
subjects affected / exposed	0 / 16 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ulnocarpal abutment syndrome
subjects affected / exposed	0 / 16 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Nalbuphine 90mg BID target dose	Nalbuphine 180 mg BID target dose	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 16 (93.75%)	8 / 8 (100.00%)	11 / 12 (91.67%)
Vascular disorders
Hot flush
subjects affected / exposed	2 / 16 (12.50%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 16 (25.00%)	2 / 8 (25.00%)	2 / 12 (16.67%)
occurrences all number	4	2	2
Somnolence
subjects affected / exposed	1 / 16 (6.25%)	0 / 8 (0.00%)	3 / 12 (25.00%)
occurrences all number	1	0	3
Headache
subjects affected / exposed	2 / 16 (12.50%)	0 / 8 (0.00%)	1 / 12 (8.33%)
occurrences all number	2	0	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 16 (25.00%)	1 / 8 (12.50%)	3 / 12 (25.00%)
occurrences all number	4	1	3
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 16 (6.25%)	0 / 8 (0.00%)	4 / 12 (33.33%)
occurrences all number	1	0	4
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 16 (12.50%)	1 / 8 (12.50%)	6 / 12 (50.00%)
occurrences all number	2	1	6
Constipation
subjects affected / exposed	2 / 16 (12.50%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	2	1	1
Diarrhoea
subjects affected / exposed	3 / 16 (18.75%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	3	0	0
Abdominal pain
subjects affected / exposed	1 / 16 (6.25%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	1	1	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	2 / 16 (12.50%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0
Skin and subcutaneous tissue disorders
Hyperhidrosis
subjects affected / exposed	1 / 16 (6.25%)	1 / 8 (12.50%)	1 / 12 (8.33%)
occurrences all number	1	1	1
Pruritus
subjects affected / exposed	1 / 16 (6.25%)	1 / 8 (12.50%)	0 / 12 (0.00%)
occurrences all number	1	1	0
Psychiatric disorders
Initial insomnia
subjects affected / exposed	1 / 16 (6.25%)	0 / 8 (0.00%)	2 / 12 (16.67%)
occurrences all number	1	0	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 16 (0.00%)	2 / 8 (25.00%)	3 / 12 (25.00%)
occurrences all number	0	2	3
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 16 (12.50%)	3 / 8 (37.50%)	1 / 12 (8.33%)
occurrences all number	2	3	1
Erysipelas
subjects affected / exposed	2 / 16 (12.50%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0
Urinary tract infection
subjects affected / exposed	2 / 16 (12.50%)	0 / 8 (0.00%)	0 / 12 (0.00%)
occurrences all number	2	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

11 Mar 2015

Protocol Amendment 1 included the following changes: • Added failure-to-improve criteria • Added post study drug discontinuation follow-up • Added substance abuse exclusion and discontinuation criteria • Provided clarity on the concomitant use of opioids • Added limits for chronic concomitant use of anti-pruritics • Added limits to histology to select sites and presented the biopsy as an optional procedure • Added a DSMB • Added central cardiac core laboratory read of study ECGs • Added exclusion criteria related to cardiac safety, as well as protocol language • Added the SOWS • Added an additional safety assessment instrument related to neurologic exam assessment • Provided clarity in the transition of subjects from the observation period to the treatment period • Provided clarity on the titration schedule and dose adjustment processes • Included gender related PK and AE information from previous studies • Incorporated EU directives • Incorporated clarifications, administrative changes, and correction of typographical errors throughout the protocol.

02 Jun 2016

Protocol Amendment 2 included the following main changes: • Increased the potential number of sites globally; Clarified the timeframe for conducting Visit 1a (including obtaining informed consent) and eligibility for study participation; Added that there could be no more than 30 days between the last dose of TR03 study drug and Visit 1a; Added that abstinent female subjects of childbearing potential could participate in the study with appropriate counseling of study requirements; Added that subjects with a serum potassium levels below the lower limit of normal at TR03 Visit 5 will be excluded and that serum potassium levels below the lower limit of normal at Visit 1a should be repeated, with supplementation provided as appropriate; Clarified that subjects must not have a QTcF interval >450ms on the Visit 1a ECG; Required that a subject’s heart rate be >50 bpm on all screening measurements. Any resting heart rate of <50 bpm was to be repeated once after 5 minutes in the supine position, and if it remained <50 bpm during the repeat, the subject was considered a screen failure; Clarified that the DSMB periodically review safety data during the time period that the blinded part of the nalbuphine HCl program remained ongoing, Required that urine pregnancy tests be performed on female subjects of childbearing potential, regardless of self-reported sexual and/or birth control status, at the required intervals per protocol; Implemented dosing compliance assessments and documentation at protocol required study visits; Clarified that paper versions of the PROs were to be administered for the study, including the Worst NRS, beginning at Visit 1a and continuing for all study visits, e-diary included; Added completion of the PAS at all study visits; Clarified the difference between the early termination subject (withdrawal of consent) and a subject with premature discontinuation of study drug treatment.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
An Open Label Extension Study of the Safety and Anti-Pruritic Efficacy of Nalbuphine HCL ER Tablets in Prurigo Nodularis Patients.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50

Primary: A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50

Primary: Treatment-Emergent Adverse Events of Special Interest

Primary: Treatment-Emergent Adverse Events of Special Interest

Secondary: Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

Secondary: Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: An Open Label Extension Study of the Safety and Anti-Pruritic Efficacy of Nalbuphine HCL ER Tablets in Prurigo Nodularis Patients.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50

Primary: A description of the incidence and nature of Treatment-emergent AEs (TEAEs) during Treatment Weeks 5 to 50

Primary: Treatment-Emergent Adverse Events of Special Interest

Primary: Treatment-Emergent Adverse Events of Special Interest

Secondary: Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

Secondary: Change From Baseline in Worst Itch Intensity NRS at Visit 2/Week 3

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 14/EOT

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

Secondary: Change From Baseline in Worst Itch Intensity NRS at VISIT 15/WASHOUT FU

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Open Label Extension Study of the Safety and Anti-Pruritic Efficacy of Nalbuphine HCL ER Tablets in Prurigo Nodularis Patients.