To assess the effect of SLT on the frequency of soft (stool of type 3, 4 or 5 on the Bristol Stool Form Scale (BSFS)) complete bowel movements (SCBMs) and SCBMs non-straining (NS) per week in subjects taking World Health Organisation (WHO) step II/…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Opioid-induced constipation and malignant and non-malignant pain
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Parameters:
* Soft Complete Bowel Movements (SCBMs) Per Week
* Soft Complete Bowel Movements-non straining (SCBMs-NS) Per Week
* Additional laxative use (including enema)
* Additional procedures (e.g. manual bowel evacuation or surgical procedure)
* Subjective Assessment of Constipation (measured by BFI)
* Compliance with SLT/opioid therapy
* SLT/ opioid-related AEs and dropouts
* Modified SOWS and COWS
* Pain Intensity Scale
* SF-36 v2 short-form health survey
* Clinical Global Impression-Improvement (CGI-I) Scale
* Patient global impression of improvement (PGI-I) Scale
* PAC QOL
* Healthcare resources used for OIC treatment
Secondary outcome
See primary parameters.
Background summary
Please see section 6.1 Therapeutic Area/Background
Study objective
To assess the effect of SLT on the frequency of soft (stool of type 3, 4 or 5
on the Bristol Stool Form Scale (BSFS)) complete bowel movements (SCBMs) and
SCBMs non-straining (NS) per week in subjects taking World Health Organisation
(WHO) step II/III opioid analgesics.
* To assess the number of subjects taking additional laxatives (including
enema) or requiring procedures (e.g. manual bowel evacuation or surgical
procedure) in addition to SLT.
* To assess symptoms of constipation in subjects taking SLT concomitantly with
WHO step II/III opioid analgesics as measured by the Bowel Function Index (BFI).
* To assess the compliance with opioids/SLT in terms of number of subjects who
did not discontinue prematurely, experience dose reduction or stop opioids/SLT
due to insufficient effect and/or intolerability.
* To assess the tolerability of SLT regarding number of subjects with
SLT-related adverse events (AEs) and dropout.
* To assess opioid withdrawal symptoms using modified Subjective Opiate
Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale (COWS) scores.
* To assess *Average Pain* over the last 24 hours at each Visit as measured by
the Pain Intensity Scale.
* To assess health status and quality of life based on the 36-Item Short Form
Health Survey (SF-36 v2* Heath Survey© (SF-36 v2)).
* To assess Patient Assessment of Constipation Quality of Life (PAC QOL).
* To assess the degree of severity of illness, changes of the Subject*s
individual status, therapeutic effect and side effects by the Investigator, as
measured on the Clinical Global Impression (CGI) severity scale, and changes in
the status of health by the subjects, as measured on the Patient Global
Impression Improvement (PGI-I) scale.
* To calculate the amount of healthcare resources used to treat the OIC.
* To assess the effect of SLT on SCBMs, SCBMs-NS and BFI in a subgroup of
subjects taking Oxycodone prolonged-release (Oxy PR) tablets.
Study design
Study Design (Methodology):
This study is a single-arm, open-label, multicentre, non-randomised, study in
subjects with chronic malignant and non-malignant pain requiring
around-the-clock WHO step II/III opioid analgesics at any dose (allowed dose as
per Summary of Product Characteristic (SmPC)), of which at least 20 subjects
(the aim is approximately 5 subjects per country) will have taken and be on
OxyContin.
The study consists of three periods: Screening (duration one week), Treatment
(duration four weeks) and Follow-up (one week). Constipated subjects who are on
WHO step II/III opioids and taking regularly at least one laxative
concomitantly for the treatment of OIC will be screened (Visit 1) according to
predefined Inclusion/Exclusion criteria. During the Treatment Period (starting
from Visit 2) subjects will be switched to standardised laxative therapy (SLT).
The SLT for this study is defined according country specific clinical practice
recommendations (see Table 4). The subjects will be monitored by the
Investigator via telephone (Visit 3 and 4) during the week following the start
of SLT for any health-related undesirable change (e.g. abdominal discomfort,
abdominal pain, abdominal cramps, diarrhoea, opioid withdrawal symptoms etc).
More telephone calls will be performed during the Treatment Period, if deemed
necessary by the Investigator. Subjects will be instructed to report every
health-related undesirable change to the Investigator by telephone.
During the Treatment Period the starting dose of WHO step II/III opioid
analgesics should be the same as established at the end of Screening Period.
Up- and down-titration is permitted according to the SmPC of the respective
opioids.
Oxycodone immediate release (OxyNorm) should ideally be analgesic rescue
medication in case of breakthrough pain for subjects receiving OxyContin. For
the remaining subjects, the use of analgesic rescue medication (opioid and
non-opioid analgesics) will be permitted at the discretion of Investigator who
will decide the type and dose of analgesic rescue medication.
Subjects will attend 5 scheduled clinic Visits (Visit 2, 5, 6, 7 and 8) and 2
telephone Visits (Visit 3 and 4) during the Treatment Period.
At the Follow-up Visit, which will be performed as a telephone Visit, safety
assessment (on-going or new AEs) and the assessment of on-going and newly
administered concomitant medications will be performed.
Intervention
The test treatment will be SLT for the treatment of OIC. If subjects take a
morning dose of pre- study laxative(s) on the day of Visit 2, the Subject
should begin taking SLT in the evening. If, in the Investigators opinion, the
SLT cannot be started on the day of Visit 2, the Subject should begin taking
SLT the following morning. The laxatives administered as part of country
specific SLT are described in protocol section 1.1 table 4.. The dosing of
laxatives (or enemas) should be in accordance with the respective SmPCs.
Study burden and risks
The protocol will follow the Dutch guidelines concerning the laxative therapy
for OIC. So the risks are the same as in normal practise. The use of laxatives
is associated with potential AEs, e.g. water and electrolyte abnormalities.
The subjects have to fill in questionnaires and diaries and have to come to the
hospital 6 times and will be contacted 3 times by phone. This will take time
what might be a burden for the subjects.
Hoehenstrasse 10
Limburg (Lahn) 65549
DE
Hoehenstrasse 10
Limburg (Lahn) 65549
DE
Listed location countries
Age
Inclusion criteria
1. Male or female subjects at least 18 years
2. Females less than one year post-menopausal must have a negative pregnancy test prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. (A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly e.g. sterilisation, implants, injectables, combined oral contraceptives, some intrauterine devices ((IUDs), hormonal), sexual abstinence or vasectomised partner).
3. Documented history of malignant or non-malignant pain that requires around-the-clock opioid therapy (WHO step II/III opioid analgesics).
4. Subjects treated with WHO step II/III opioid analgesics for at least 2 weeks prior to Screening Visit (Visit 1), who will continue with the opioid(s) over the proposed study period.
5. Subjects meeting the following criteria for OIC:
* Subject and Investigator confirm that the Subject*s constipation is induced, or worsened by the Subject*s opioid medication (present at Screening)
* Subjects with mean BFI score > 30 at Visit 1
* Subjects with < 3 complete bowel movements (CBMs) in the week preceding the Visit 1, based on Subject*s retrospective memory in response to Investigator*s question
6. Subjects taking at least one laxative on regular basis (i.e. *2 intakes per week during the *2 weeks prior to screening) for the treatment of OIC.
7. Subjects must be willing to take SLT.
8. Subjects taking daily natural dietary fibre supplementation are eligible if they can maintain their diet throughout the study, and in the Investigator*s opinion are willing and able to maintain adequate hydration.
9. Subjects must be willing and able (e.g. mental and physical condition) to participate in all aspects of the study, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent.
10. In the Investigator*s opinion the Subject*s concomitant medication dose will remain stable throughout the study Period (here concomitant medications mean all medications besides opioids (standard and rescue opioid treatment)).
Exclusion criteria
Medical Conditions:
1. In the Investigator*s opinion any contraindication and precautionary condition for laxative medication(s) used in the study as per the SmPC.
2. Subjects having any potential non-opioid cause of constipation that might be a major contributor to the constipation (Refer to Appendix 18.4 for examples).
3. Surgery within 2 months prior to the start of the Screening Visit (Visit 1), or planned surgery during the Screening and Treatment periods that may affect GI motility.
4. Subjects with colostomy or ileostomy.
5. Hospitalisation expected/planned within the study Period (e.g. planned hospitalisation for the treatment of a pre-existing condition before informed consent) which can affect the outcome measure analysis.
Treatments/Medications:
6. Subjects presently taking, or who have taken opioid antagonist (e.g. naloxone, naltrexone and methylnaltrexone) or opioid antagonists containing products (e.g. oxycodone/naloxone, buprenorphine/naloxone, pentazocine/naloxone, tilidine/naloxone) * 30 days prior to the start of the Screening Period.
7. Subjects already taking maximum daily dose of country specific SLT (both First and Second Line SLT) on a regular basis (i.e. *4 days per week) for the treatment of OIC.
8. Subjects receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine).
Additional Screening Exclusion Criteria for Subjects Suffering from Non-malignant Pain:
9. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as Visit 1).
Additional Screening Exclusion Criteria for Subjects Suffering from Malignant Pain:
10. Subjects who have received a new chemical entity or an experimental drug within 30 days of study entry (defined as Visit 1). Concurrent participation in another clinical trial is not permitted except the epidemiological study performed to assess the long-term survival data.
11. Subjects with an expected life expectancy of *3 months.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000180-81-NL |
| CCMO | NL44941.075.13 |