Clinical Trial Results:
A randomized , double-blind, placebo-controlled study of antidepressant effects of the endogen compound neuropeptide y (NPY) in patients suffering from major depressive disorder
Summary
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EudraCT number |
2014-000129-19 |
Trial protocol |
SE |
Global end of trial date |
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Oct 2022
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First version publication date |
26 Oct 2022
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Other versions |
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Summary report(s) |
Abstract NPY abstract on MIRANDA npy attachment one |
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 |
NPY
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Karolinska Institute, d
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Sponsor organisation address |
Solnavägen 1, Stockholm, Sweden, 17177
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Public contact |
Aleksander Mathé, MD, PhD, Senior Professor, Karolinska University Hospital, Huddinge, +46 704840743, aleksander.mathe@ki.se
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Scientific contact |
Aleksander Mathé, MD, PhD, Senior Professor, Karolinska University Hospital, Huddinge, +46 704840743, aleksander.mathe@ki.se
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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 |
Interim
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Date of interim/final analysis |
14 Feb 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Feb 2020
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
study if NPY decreases symptoms of depression
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Protection of trial subjects |
Institutional review board (EPN, Regionala Etikprövningsnämnden i Stockholm, Dnr 2014/582- 31/2 and 2015/1233-32)
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Background therapy |
none | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Aug 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
30
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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 |
Participants were recruited by the Karolinska Trial Alliance via advertisement, who also monitored the trial. All participants signed the informed consent form. | |||||||||
Pre-assignment
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Screening details |
At the screening visit, participants met the study physician who took the medical history and performed a physical examination. ECG and vital signs were recorded; urine toxicology and an alcohol breath test were taken. Safety blood samples were drawn and a pregnancy test taken. Prior and concomitant medications were documented. Nov-15 to Oct-17 | |||||||||
Pre-assignment period milestones
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Number of subjects started |
30 | |||||||||
Number of subjects completed |
30 | |||||||||
Period 1
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Period 1 title |
Trial (overall period)
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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, Carer, Assessor | |||||||||
Blinding implementation details |
The list of random treatment assignments was set up according to the random permuted blocks method with blocks of 10 patients. NPY and placebo were prepared by an independent person not otherwise involved in any of the study procedures. A randomization list was only available to the independent person preparing the study drug. All other study personnel were blind to treatment assignment. Code envelopes were available at the study site in case the treatment blind needed to be broken for eme
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NPY experimental drug | |||||||||
Arm description |
NPY | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
NPY
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for nebuliser solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
s. On the day of the experiment, the designated pharmacist who was not otherwise involved in any of the study procedures (APL, Pharmacy,
Steriltillverkningen Karolinska Solna) prepared the NPY (6,8 mg) or placebo in sterile water and delivered the unmarked syringes to
the person responsible for experimental solution administration with the ViaNase Electronic Atomizer (Kurve Technology
Inc, Bothel, WA).
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Arm title
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Placebo | |||||||||
Arm description |
Placebo intranasal spray | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
sterile water
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for nebuliser solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
s. On the day of the experiment, the designated pharmacist who was not otherwise involved in any of the study procedures (APL, Pharmacy,
Steriltillverkningen Karolinska Solna) prepared the NPY or placebo in sterile water and delivered the unmarked syringes to
the person responsible for experimental solution administration with the ViaNase Electronic Atomizer (Kurve Technology
Inc, Bothel, WA)
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Investigational medicinal product name |
sterile water
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for nebuliser solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
s. On the day of the experiment, the designated pharmacist who was not otherwise involved in any of the study procedures (APL, Pharmacy,
Steriltillverkningen Karolinska Solna) prepared the NPY (6,8 mg) or placebo in sterile water and delivered the unmarked syringes to
the person responsible for experimental solution administration with the ViaNase Electronic Atomizer (Kurve Technology
Inc, Bothel, WA).
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Baseline characteristics reporting groups
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Reporting group title |
Trial
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Reporting group description |
NPY and Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
NPY experimental drug
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Reporting group description |
NPY | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo intranasal spray | ||
Subject analysis set title |
MADRS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Primary Outcome: MADRS—Changes in MADRS score by group within the 48 hours post NPY insufflation are presented in Figure 1 and Tables 2 and 3. NPY was superior to placebo in reducing MADRS score at 24 hours posttreatment; decrease of 10.3 points (95% CI: −13.5; −6.8) vs decrease of 5.6 points (95% CI: −8.4; −2.7), respectively (group*time interaction F=3.26 DF=(1,28), P=.04; Cohen’s d=0.67). There was a similar trend toward benefit of NPY over placebo at +1 hour (decrease of 5.7 points [95% CI: −8.5; −2.8] vs decrease of 3.8 points [95% CI: −6.2; −1.5]; group*time interaction F = 0.71 DF = (1,28), P = .20) and at +5 hours (decrease of 7.1 points [95% CI −10.0; −4.2] vs decrease of 3.5 points [95% CI: −5.8; −1.2]; group*time interaction F=2.69, DF=(1,28), P=.05; Cohen’s d=0.61). At +48 hours there was no longer a separation between NPY and placebo (decrease of 8.3 [95% CI: −12.5; −4.3] vs 8.5 points [95% CI: −11.8; −5.2]; group*time interaction F = 0.0001, DF = (1,28), P = .49).
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End point title |
24 h post inhalation | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
24 hours after inhalation
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Notes [1] - NPY [2] - Placebo |
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Statistical analysis title |
MADRS | ||||||||||||
Statistical analysis description |
Analytic approach—Two-way ANOVA for repeated measures,
Mann-Whitney U test, and Wilcoxon Matched Pairs test were
used. Homogeneity of variances was examined using boxplots and Levene’s test. P<.05 was considered significant. Since
this was designed as an early-phase proof of concept study,
there was no adjustment planned for multiplicity.
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Comparison groups |
Placebo v NPY experimental drug
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.5 | ||||||||||||
Method |
ANOVA | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Duration of experiment, 5 days
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
18.0
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Frequency threshold for reporting non-serious adverse events: 1% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no adverse events recorded during the course of the trial |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
Enrollment ended early, at n=30, due to un-anticipated limitation of drug supply |