Clinical Trial Results:
A phase IIa study of GR3027 in patients with idiopathic hypersomnia (IH) involving an open-label part to assess safety, tolerability and pharmacokinetics (PK) of a single oral GR3027 dose in female patients and a randomized, double-blind, placebo-controlled crossover study to assess safety, tolerability, exposure and exploratory efficacy of multiple oral doses of GR3027 in male and female IH patients.
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Summary
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EudraCT number |
2017-002127-16 |
Trial protocol |
FI DK SE |
Global end of trial date |
19 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Nov 2019
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First version publication date |
03 Nov 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
UCAB-CT-03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Umecrine Cognition AB
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Sponsor organisation address |
Fogdevreten 2, Solna, Sweden, 171 65
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Public contact |
Chief Executive Officer, Umecrine Cognition AB, 46 852484484, magnus.doverskog@umecrine.com
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Scientific contact |
Chief Executive Officer, Umecrine Cognition AB, 46 852484484, magnus.doverskog@umecrine.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Nov 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Oct 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Part A: The primary objective is to assess the safety and tolerability of GR3027 after a single oral dose of GR3027 in female patients with IH.
Part B: The primary objective is to assess the safety and tolerability of GR3027 after multiple dose administration in patients with IH.
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Protection of trial subjects |
The protocol and the statement of informed consent were approved in the respective countries by an Independent Ethics Committee (IEC) prior to each centre's initiation. The trial was conducted in accordance with the Declaration of Helsinki and its revisions as well as with the valid local and national law(s), with the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP) (E6) issued in July 1996, and with the Commission Directives 2001/20/EC, 2005/28/EC and 2001/83/EC. Written Informed Consent was received from all subjects prior to enrolment into the trial, as dictated by the Declaration of Helsinki.
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Background therapy |
None | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
01 Sep 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 2
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Country: Number of subjects enrolled |
Denmark: 3
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Country: Number of subjects enrolled |
Finland: 5
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment was initiated in Sept 2017 and was done simultaneously in FI, DK and SE | |||||||||
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Pre-assignment
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Screening details |
Female patients 18 to 55 years with a diagnosis of IH and with no current treatment for hypersomnolence disorder were enrolled in the study. There was a wash-out period of 14 days before randomization to study treatment. | |||||||||
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Period 1
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Period 1 title |
Overall study (overall period part B)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
Blinding implementation details |
The investigators, staff at the trial sites, trial monitors, and data analysis/management personnel were blinded to the subject assignment in order to ensure that information that could potentially bias handling of data was not disclosed.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sequence: GR3027-Placebo | |||||||||
Arm description |
Randomized subjects received GR3027 in the first study period (Day 1-14) and placebo in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
GR3027
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
8 capsules received twice daily for 14 days
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Investigational medicinal product name |
GR3027 Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
8 capsules twice daily for 14 days
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Arm title
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Sequence: Placebo-GR3027 | |||||||||
Arm description |
Randomized subjects received Placebo in the first study period (Day 1-14) and GR3027 in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
GR3027
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
8 capsules of 80 mg twice daily for 14 days
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Investigational medicinal product name |
GR3027 Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
8 capsules twice daily for 14 days
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Baseline characteristics reporting groups
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Reporting group title |
Sequence: GR3027-Placebo
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Reporting group description |
Randomized subjects received GR3027 in the first study period (Day 1-14) and placebo in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sequence: Placebo-GR3027
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Reporting group description |
Randomized subjects received Placebo in the first study period (Day 1-14) and GR3027 in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sequence: GR3027-Placebo
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Reporting group description |
Randomized subjects received GR3027 in the first study period (Day 1-14) and placebo in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | ||
Reporting group title |
Sequence: Placebo-GR3027
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Reporting group description |
Randomized subjects received Placebo in the first study period (Day 1-14) and GR3027 in the second study period (Day 1-14). There was a 7 days wash-out period between study treatments. | ||
Subject analysis set title |
GR3027 (Full Analysis Set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set included all subjects who were randomized and received study treatment.
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Subject analysis set title |
Placebo (Full Analysis Set)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Full analysis set included all subjects imho were randomized and received study treatment.
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End point title |
ESS | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to end of study treatment period (14 days)
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Statistical analysis title |
Mixed model analysis | ||||||||||||
Statistical analysis description |
The mixed model analysis for ESS included baseline as a fixed effect. No other baseline covariates were adjusted for in the model. The significance level was not adjusted for multiple inferential tests, and type I error was therefore not be controlled, which is considered acceptable for exploratory efficacy evaluations. P-values below 0.05 were considered nominally statistically significant.
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Comparison groups |
GR3027 (Full Analysis Set) v Placebo (Full Analysis Set)
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.04
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.27 | ||||||||||||
upper limit |
2.36 | ||||||||||||
| Notes [1] - P-values below 0.05 were considered nominally statistically significant. |
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End point title |
MWT | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to end of study treatment (14 days)
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Statistical analysis title |
Mixed model analysis | ||||||||||||
Statistical analysis description |
The mixed model analyses for MWT included baseline as a fixed effect. No other baseline covariates were adjusted for in the model.The significance level was not adjusted for multiple inferential tests, and type I error was therefore not be controlled, which is considered acceptable for exploratory efficacy evaluations. P-values below 0.05 were considered nominally statistically significant.
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Comparison groups |
GR3027 (Full Analysis Set) v Placebo (Full Analysis Set)
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority [2] | ||||||||||||
P-value |
≤ 0.05 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
3.63
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.76 | ||||||||||||
upper limit |
8.03 | ||||||||||||
| Notes [2] - P-values below 0.05 were considered nominally statistically significant. |
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Adverse events information
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Timeframe for reporting adverse events |
From start of study treatment at Day 1, up to 14 days after end of study treatment in period 2
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Adverse event reporting additional description |
An adverse event (AE) was any untoward medical occurrence in a subject administered the study treatment (GR3027 or placebo) which did not necessarily have a causal relationship with the study treatments
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
GR3027
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Reporting group description |
Randomized subjects for the sequence GR3027 - Placebo received GR3027 in the first study period (Day 1-14) and placebo in the second study period Day 1-14. There was a 7 days wash-out period between treatments. Randomized subjects for the sequence Placebo - GR3027 received placebo in the first study period (Day 1-14) and GR3027 in the second study period Day 1-14. There was a 7 days wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Randomized subjects for the sequence GR3027 - Placebo received GR3027 in the first study period (Day 1-14) and placebo in the second study period Day 1-14. There was a 7 days wash-out period between treatments. Randomized subjects for the sequence Placebo - GR3027 received placebo in the first study period (Day 1-14) and GR3027 in the second study period Day 1-14. There was a 7 days wash-out period between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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29 Jan 2018 |
Clarification and change of inclusion criteria |
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14 Mar 2018 |
Update of exclusion criteria |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
