The objective of this exploratory study is to investigate the acid neutralisation action of sodium alginate oral suspension versus placebo liquid, within the stomach and to assess suitability and robustness of the pH monitoring methodology.
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Brief title
Condition
- Other condition
Synonym
Health condition
GORD
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be the mean percentage of time that pH >= 4 over 0-30
minutes post-dose across electrodes 3 to 10. The primary analysis will be the
comparison of this endpoint between Sodium alginate oral suspension versus
placebo liquid.
Secondary outcome
• The mean percentage of time that pH >= 4 over the interval 30-60 minutes
post-dose across electrodes 3 to 10.
• The mean percentage of time that pH >= 3 over the intervals 0-30 minutes and
30-60 minutes post-dose across electrodes 3 to 10.
• The mean percentage of time that pH >= 3 and pH >= 4 over the 10 minute
intervals post-dose across electrodes 3 to 10.
• The percentage of time that pH >= 3 and pH >= 4 over the 10 minute and 30
minute intervals at each electrode.
These endpoints will be compared between Sodium alginate oral suspension and
placebo. For calcium carbonate / magnesium carbonate chewable tablets, these
endpoints will be assessed non-comparatively.
For all treatments, the following will be displayed non-comparatively:
• The pH level at each 4 second time point during each monitoring period at
each electrode.
Background summary
This exploratory study is being conducted to characterise the acid
neutralisation activity of Sodium alginate oral suspension versus a liquid
placebo, in order to confirm robustness of the methodology being used and to
develop appropriate endpoints for a future confirmatory study.
In addition, to confirm that the methodology is suitable, a small cohort of
subjects will receive a single maximum dose of calcium carbonate / magnesium
carbonate chewable tablets (two tablets). The results from this cohort will be
used to confirm robustness of the methodology in order to enable preparations
for a further exploratory study in Sodium alginate tablets.
The effects of acid neutralisation can be observed in a healthy stomach,
therefore, to minimise risk to patients, healthy volunteers of both genders
will be used. Previous research within this field has successfully
demonstrated the effects of acid neutralisation in vivo. To align with previous
research and reduce variablility caused by the post prandial gastric buffering
effect, a fasted stomach will be investigated in this study. A single, maximum
dose of Investigational Medicinal Product (IMP) should be sufficient to
demonstrate the antacid activity of the product and therefore only a single
maximum dose will be given in the study. Subjects will be randomised to receive
either liquid or tablet, they will not receive both medications.
The liquid cohort of the study uses a cross-over design to minimise an
individual*s variation in stomach response, so each subject of this group will
receive in a randomised order 20 mL Sodium alginate oral suspension or 20 mL
placebo liquid in each treatment period. The tablet cohort will only receive 2
calcium carbonate / magnesium carbonate chewable tablets orally. These routes
of administration and dosages are approved in the summary of product
characteristics (SmPC).
This study will use a custom-designed CE marked catheter that has been
specifically designed and made for this study, containing 10 pH electrodes.
This catheter will measure pH from 5 cm above to 16 cm below the Squamocolumnar
Junction (SCJ).
Study objective
The objective of this exploratory study is to investigate the acid
neutralisation action of sodium alginate oral suspension versus placebo liquid,
within the stomach and to assess suitability and robustness of the pH
monitoring methodology.
Study design
There will be two groups in this study.
Group I will be a randomised, crossover, open label, single-dose, placebo
controlled study, to characterise the antacid activity of Sodium alginate oral
suspension (20 mL) in healthy volunteers, using a custom-designed intragastric
and oesophageal pH catheter. Subjects and clinic staff will remain open label
to medications administered, with the consultant gastroenterologist blinded to
medication allocation, in order to be unbiased when assessing catheter
positioning during pH recording periods.
In addition, a separate, small cohort of subjects (Group II) will be used to
assess the suitability of the pH monitoring methodology. These subjects will
receive a single maximum dose of calcium carbonate / magnesium carbonate
chewable tablets (2 tablets) and will undergo the same pH monitoring procedures
as subjects of Group I.
Sodium Alginate Oral Suspension Cohort (Group I)
Subjects will attend the clinic for four visits (one screening, two dosing and
one follow up visit). There will be a minimum 5 days and a maximum 14 days
washout period between dosing in the two treatment visits. The follow up will
be performed 3-7 days after the second dosing day.
Calcium Carbonate / Magnesium Carbonate Chewable Tablet Cohort (Group II)
As there will be no cross-over element to this part of the study subjects will
only attend the clinic for three visits (one screening, one dosing and one
follow up visit). The follow up will be performed 3-7 days after the dosing
day.
Intervention
The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), an alcohol breath test, urine drug screen, a physical
examination and a vital signs measurement will be performed.
After the subject passes all above mentioned tests, the subject will be
enrolled in the study.
During study the subjects will enter the clinic and will receive 1 or 2
medication formulations (pending enrollment group 1 or 2), subjects will be
asked on a regular basis for possible side effects and the vital signs will be
checked on a regular basis.
On day 1 of each period a pH catheter (a thin flexible tube containing sensors
to measure the acidity in the stomach) will be inserted. in addition an
endoscopy will performed confirming correction positioning of the catheter.
Movement of the subject is restricted during the pH monitoring procedure.
Finally a follow-up examination will be performed. During this visit the
subjects will be asked for possible side effects, blood will be drawn for
safety, the vital signs will be checked and a physical examination will be
performed.
Study burden and risks
There have been side effects reported with the study medications. The
side-effects that are reported and are possibly related to administration of
sodium alginate or calcium carbonate products include allergic manifestations
such as urticaria (hives), bronchospasm (difficulty in breathing), angioedema
(swelling of the skin), abdominal pain/discomfort, pruritus rash (itchy skin),
diarrhoea, nausea, vomiting, an allergic-like reaction and acute very severe
allergic reactions in the whole body as a result of hypersensitivity to any of
the active substances (sodium alginate, sodium bicarbonate and calcium
carbonate) or to any of the excipients (e.g. hydroxybenzoates). Other side
effects include muscular weakness, hypermagnesaemia (increased levels of
magnesium in the blood), hypercalcaemia (increased calcium levels in the
blood), alkalosis (disturbance in acidity in the body), acid rebound or
constipation. Furthermore, milk alkali syndrome (excessive calcium amount in
blood) can cause ageusia (loss of taste functions of the tongue), headache,
azotemia (an increase in urea or creatinine in the blood), asthenia (weakness)
and calcinosis (formation of calcium deposits in soft tissue).
The risks are limited in healthy participants, but you may experience one of
the above mentioned side-effects or other symptoms not previously reported. To
keep the risks as low as possible, your health will be closely monitored during
the trial to minimize these risks.
In total, two blood samples will be drawn. The total blood volume will be 16
mL. The blood collection procedure is not dangerous, but may cause discomfort
or bruising. Occasionally, fainting or an infection at the blood sampling site
can occur.
The nasal endoscopy and catheter insertion procedures are not painful. In
general, it is described as an uncomfortable feeling. During the procedure
there is a small risk to develop bleeding and perforation of the oesophagus,
stomach or duodenum. In addition, reactions to drugs administered as part of
the procedure can occur, for example to the local anaesthetics. The risk of one
of these side-effects to occur is considered to be low, as the insertion of the
catheter can be verified visually by a small camera.
Dansom Lane -
Hull HU8 7DS
GB
Dansom Lane -
Hull HU8 7DS
GB
Listed location countries
Age
Inclusion criteria
1) Informed consent has been obtained.
2) Age: >= 18 years <= 50 years.
3) Sex: male or female subjects.
4) Status: healthy subjects.
5) Body Mass Index (BMI): >= 18.5 and <= 24.9
Exclusion criteria
1) A history of gastro-oesophageal reflux or active gastrointestinal disease (gastroduodenal ulcer, gastrointestinal haemorrhage, mechanical obstruction or perforation) within the last year.
2) Clinically significant allergic, pulmonary, neurological, renal, hepatic, cardiovascular, psychiatric, metabolic, endocrine, or haematological disease.
3) A history of basal skull fracture or who have undergone trans-sphenoidal surgery.
4) Have been hospitalised within the previous three months for major surgery or medical illness.
5) A clinically significant illness within the 4 weeks prior to screening.
6) Have taken any prescription medication or non-prescription medication within the last seven days, prior to the screening visit, which the Principal Investigator considers may interfere with the study.
7) Have taken antacids, H2 antagonists, motility stimulants (e.g. prokinetics, macrolide antibiotics such as erythromycin and azithromycin, and 5HT agonists such as sumatriptan) or other medicines for relief of symptoms of acid reflux disease 2 weeks prior to enrolment in the study and during the study and/or have taken proton pump inhibitors 4 weeks prior to enrolment into the study and during the study. Enrolment is defined as the date of informed consent signature.
8) Are taking any of the following medications: antihistamines, tetracyclines, digoxin, fluoroquinolone, iron salt, neuroleptics, thyroxine, penicillamine, beta-blockers (atenolol, metoprolol, propranolol), glucocorticoid, chloroquine, and biphosphonates.
9) Have a drug hypersensitivity, which in the opinion of the Principal Investigator might interfere with the study.
10) Any previous history of allergy or known intolerance to any of the Investigational Medicinal Product*s (IMP) or following formulation constituents: e.g. sodium alginate, parabens (methyl and propyl), glucose syrup, carbomer, and xanthan gum
11) Those with known hypophosphataemia.
12) Those on a highly restricted salt diet.
13) Those with, or a history of, hypercalcaemia, nephrocalcinosis and recurrent calcium containing renal calculi.
14) A current or recent (within one year) history of alcohol abuse or significant abuse of any legal or illegal drugs, substances and solvents.
15) Regularly (weekly) consume excessive amounts of alcohol (> 8 units for men and > 6 units for women in one consumption, excessive amounts as defined by the UK National Office of Statistics).
16) Have consumed more than 2 units of alcohol per day in the 7 days prior to the screening visit.
17) Regular consumption of excessive quantities of caffeine (> 6 cups of tea, coffee or cola per day), according to the Investigator*s judgement.
18) Tobacco use is > 6 cigarettes per day or equivalent or unable to refrain from tobacco/ nicotine use during the study periods.
19) Any clinically significant abnormal laboratory result, in the opinion of the Principal Investigator.
20) Female subjects of childbearing potential who, for the duration of the study, are either unwilling or unable to take adequate contraceptive precautions (as defined in the protocol or are unwilling to be sexually abstinent (as defined in the protocol).
21) Pregnancy or lactating mother.
22) Are unable to communicate well with the Investigator (i.e. language problem, poor mental development or impaired cerebral function) in the opinion of the Investigator.
23) Those previously randomised into this study.
24) Employee at study site.
25) Partner or first-degree relative of the Investigator.
26) Participation in a clinical study in the previous 3 months.
27) Those unable in the opinion of the Investigator to comply fully with the study requirements.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003158-15-NL |
| CCMO | NL50419.056.14 |