Clinical Trial Results:
A pilot study of Aripiprazole treatment for antipsychotic induced hyperprolactinaemia in young patients with severe mental illness and learning disabilities.
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Summary
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EudraCT number |
2009-011228-73 |
Trial protocol |
GB |
Global end of trial date |
31 Dec 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Sep 2016
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First version publication date |
21 Sep 2016
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Other versions |
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Summary report(s) |
Aripiprazole and Prolactin Study |
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 |
OCTUMI-03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01085383 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Oxford
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Sponsor organisation address |
Clinical Trials and Research Governance, Block 60, Churchill Hospital, Old Road, Oxford, United Kingdom, OX3 7LE
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Public contact |
Dr Valeria Frighi, Dr. Valeria Frighi
University of Oxford, 44 1865223779, valeria.frighi@psych.ox.ac.uk
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Scientific contact |
Dr Valeria Frighi, Dr Valeria Frighi
University of Oxford, 44 1865223779, valeria.frighi@psych.ox.ac.uk
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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 |
03 Aug 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Dec 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Can addition of aripiprazole to current antipsychotic normalize or reduce prolactin sufficiently to restore normal function of the ovaries and the testes?
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Protection of trial subjects |
Trial procedures were minimal, namely measuring of height and weight, and blood sampling. Trial subjects were asked during the visit at which stage they would like to have their physical measurements and the blood sample taken, and their wishes were followed. Additionally, for participants with a learning disability, a trusted carer was always present, so that any potential distress was minimised.
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Background therapy |
There were no treatments that were not tests or comparator products which were used across all groups in the trial. | ||
Evidence for comparator |
All patients in the trial were using an antipsychotic medication causing hyperprolactinaemia. These antipsychotics were risperidone, paliperidone, amisulpride and sulpiride. However, it became apparent during the trial and on review of the literature, that the response to the test drug aripiprazole, was different according to whether participants were taking risperidone or paliperidone or were taking amisulpride or sulpiride. Because of this, analyses were carried out by comparing the two groups of patients. | ||
Actual start date of recruitment |
27 Apr 2011
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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 |
United Kingdom: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
15
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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) |
2
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Adults (18-64 years) |
13
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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 took place between September 2010 and June 2014. It was very prolonged due to the unexpected paucity of referrals of patients with known or suspected antipsychotic-induced hyperprolacytinaemia by local psychiatrists and General Practitioners, and to a high exclusion rate. 15 patients were recruited. | ||||||||||||
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Pre-assignment
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Screening details |
70 patients were referred to the study. 55 of these were excluded due to patient's refusal (8) or legal representative's refusal (1), normal prolactin (11), regular periods (7), menopause (3), use of sex hormones treatment (4), normal testosterone (14), primary gonadal failure (5), uncontrolled diabetes (2). | ||||||||||||
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Period 1
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Period 1 title |
Baseline period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
The study was not blinded.
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Arms
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Arm title
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Aripiprazole | ||||||||||||
Arm description |
There is only one arm as this is an uncontrolled intervention study (each participant serves as their own controls as changes are measured according to dose of drug received). | ||||||||||||
Arm type |
single arm | ||||||||||||
Investigational medicinal product name |
Aripiprazole
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Investigational medicinal product code |
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Other name |
Abilify
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Pharmaceutical forms |
Buccal tablet, Oral drops, solution
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Routes of administration |
Oral use
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Dosage and administration details |
Aripiprazole was administered at a dose of 1.5 to 10 mg daily according to prolactin response. It was taken by participants as a tablet or oral solution in a once daily administration in the morning, after food.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Subjects completing trial (baseline prolactin values)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
These are the subjects who completed the trial, namely those who reached a stable dose of aripiprazole and in whom therefore efficacy analysis could be done, when their prolactin was measured before starting aripiprazole.
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Subject analysis set title |
Subjects completing trial (prolactin values on aripiprazole)
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
These are the subjects who completed the trial, namely those who reached a stable dose of aripiprazole and in whom therefore efficacy analysis could be done, when their prolactin was measured during follow-up at a stable aripiprazole dose.
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End points reporting groups
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Reporting group title |
Aripiprazole
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Reporting group description |
There is only one arm as this is an uncontrolled intervention study (each participant serves as their own controls as changes are measured according to dose of drug received). | ||
Subject analysis set title |
Subjects completing trial (baseline prolactin values)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
These are the subjects who completed the trial, namely those who reached a stable dose of aripiprazole and in whom therefore efficacy analysis could be done, when their prolactin was measured before starting aripiprazole.
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Subject analysis set title |
Subjects completing trial (prolactin values on aripiprazole)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
These are the subjects who completed the trial, namely those who reached a stable dose of aripiprazole and in whom therefore efficacy analysis could be done, when their prolactin was measured during follow-up at a stable aripiprazole dose.
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End point title |
Decrease in Prolactin | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Decrease in Prolactin between baseline and following aripiprazole up-titration
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Statistical analysis title |
Related samples Mann-Whitney U test | ||||||||||||
Statistical analysis description |
Prolactin levels at baseline were compared with prolactin levels achieved following up-titration of aripiprazole
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Comparison groups |
Subjects completing trial (baseline prolactin values) v Subjects completing trial (prolactin values on aripiprazole)
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Number of subjects included in analysis |
24
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.004 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Median difference (net) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Duration of the trial
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Adverse event reporting additional description |
Information about aripiprazole related adverse events and Serious Adverse Events (whether or not study drug related) was collected at each study visit.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
SNOMED CT | ||||||||||||||||||||||||||||||||||||
Dictionary version |
2016
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Reporting groups
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Reporting group title |
Aripiprazole
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Reporting group description |
There is only one arm as this is an uncontrolled intervention study (each participant serves as their own controls as changes are measured according to dose of drug received). | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.01% | |||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Feb 2012 |
The age range was amended from 16 to 25 years originally to 16 years and above. Subjects lacking capacity for informed consent were included. The starting dose of aripiprazole was reduced to 2.5 mg and the up-titration schedule modified to 2.5 mg step increases. We specified that the study was open to patients with learning disabilities and patients with any type of severe mental illness, rather than only schizophrenia, requiring long-term antipsychotic treatment.
The rationale of some of these changes was to increase the number of patients recruited, to make the study more relevant to patients with a learning disability as many of them lack capacity to consent, and to include any patients on chronic antipsychotic therapy. The changes in dose were due to the publication of a study showing efficacy of low dose aripiprazole and to the clinical experience of the study investigators. |
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28 Aug 2012 |
Recruitment to the study via General Practitioners was added to recruitment via psychiatrists. This was done in order to increase the number of trial patients. |
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03 Feb 2014 |
Modification of the duration of follow-up from a total of two years to a minimum of six months and maximum of 2 years.
The rationale for this change was that recruitment had been very difficult and therefore we wished to maximise our potential to include participants. As a consequence, recruitment would be continued for a sufficient time period to reach the primary outcome of the study (namely the reduction in prolactin level), which, when achieved, occurs within six months of starting the study drug. There would be insufficient follow-up time to investigate changes in bone mineral density, the secondary outcome of the study. However, there would be no practical consequences, as in the study we found no patients actually requiring a bone mineral density scan after two years from baseline.
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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 | |||
