Data on 14C-urea

Structural Formula (14C-urea): NH2 14CONH2

Radiation emission: beta-emission, 49 keVmean, 156 keVmax, no other emissions

External emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.

Radiological Half-life: 5730 years

Maximum effective dose equivalent (EDE) : 0.3 mrem/µCi

STUDY 1

Of 186 patients who had histopathology and CLOtest1 (80 men, 106 women), 53 were infected with H.pylori as determined by agreement between histology and CLOtest1. The study results are summarized below:

STUDY 2

Breath tests were performed on 436 outpatients attending gastroenterology practices at sites in the United States. Seventy-six patients (40 men, 36 women) who had histology and CLOtest1 were evaluated. The results are summarized below:

General

After the patient ingests the 14C-urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.

A false positive test could occur in patients who have achlorhydria. Very rarely, a false positive test may occur due to urease associated with Helicobacters other than H.pylori (i.e. Helicobacter heilmanni).

Limitations of the Test

• The test has been evaluated in outpatients before elective endoscopy.
• Test results should be evaluated with clinical signs and patient history when diagnosing H.pylori infection.
• The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H.pylori infection.
• A negative result does not completely rule out the possibility ofH.pylori infection. If clinical signs and patient history suggest H.pyloriinfection, repeat the PYtest1 or use an alternative diagnostic method.
• The integrity of samples in balloons sent by air transport has not been adequately determined. In studies simulating the effects of air transport for two to seven days at temperatures of -40°C, 20°C and 55°C, no balloon failures were observed. However, the data could not provide statistical determination that no changes in 14CO2concentration took place.
• For ground transport, integrity of samples in balloons has not been determined beyond 7 days. During this time frame, concentration of labeled CO2 can decrease as much as 0.36% per day.

Radioactivity

Persons concerned about very low doses of radioactivity may postpone the test or may decide to use an alternative means of diagnosis. The test produces radiation exposure equal to 24 hours of normal background. In animal experiments, such low doses of radiation do not carry measurable risk.

Preclinical studies were not conducted on 14C-urea. The estimated dose equivalent received from a single administration of PYtest1 (1µCi 14C) is about 0.3 mrem.

Information for Patients

It is necessary for the patient to fast for 6 hours before the test. The patient should also be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.

Carcinogenesis, mutagenesis, impairment of fertility

No studies have been conducted with 14C-urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.

Drug Interactions

Antibiotics, proton pump inhibitors, sucralfate, and bismuth preparations are known to suppress H.pylori. Ingestion of antibiotics or bismuth within 4 weeks and proton pump inhibitors or sucralfate within 2 weeks prior to performing the test may give false negative results.

Pregnancy

Nursing mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest1 is administered to a nursing woman.

Pediatric Use

Clinical studies in children have not been conducted. However, PYtest1 is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into a straw.

Materials provided

As shown in Figure 2, the PYtest1 Kit contains:

• PYtest1 capsule
• Two 30 mL disposable cups
• One drinking straw
• One mylar collection balloon
• One report form
• One mailing box with labels2

Figure 2: PYtest1 Kit

2

The kit includes analysis by Kimberly-Clark of one balloon from one patient at one time point.

Materials Needed but not Provided

1. Stopwatch/Timer capable of timing an interval up to 10 minutes.
2. Water (40mL)

Dosage

One PYtest1 capsule.

Procedural Notes

• Inform the patient to fast for 6 hours prior to the test.
• The patient should be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test.
• Have patient sitting at rest while doing the test.
• The capsule should not be handled directly as this may interfere with the test result.
• To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.

Step by Step Procedure for Balloon

Quality Control

A minimum of 1 mM of CO2 is required to perform analysis of a breath sample. The amount of breath required to provide 1 mM of CO2varies depending on the amount of CO2 the patient is producing. Since a full balloon typically contains at least 1 mM of CO2, the balloon should be completely filled.

Results

The indeterminate result should be evaluated by repeating the PYtest1or using an alternative diagnostic method. If repeat breath testing is undertaken, careful history to exclude confounding factors should be obtained. If confounding factors are present, wait an appropriate time (refer to Table 4) before repeating the PYtest1.

The cutoff point of 50 DPM was determined to be the mean + 3SD of results obtained in patients who did not have H.pylori.

DPM = Disintegrations per minute

Expected Values

As shown in Figure 3 approximately 30% of patients tested will be positive for H.pylori.

Figure 3: Histogram showing DPM distribution for the PYtest1.

Note: DPM groupings were calculated on a logarithmic scale. Empty DPM groupings were not included. Chart includes all patients from Studies 1 and 2.

Frequency of DPM group includes samples with DPM < Group Name.

     DPM = Disintegrations per minute

     Gold Standard = Agreement between histology and CLOtest1

If the capsule is damaged or appears abnormal in any way, it may give inaccurate results.

PYtest1 Capsules and Kit should be stored at 15°-30°C (59°-86°F) in an area designated by each individual institution's regulations.

Rx Only