PYtest

Avent, Inc.

PYtest Kit (C-Urea Breath Test)

FULL PRESCRIBING INFORMATION: CONTENTS*

• Description
  • Data on C-urea
• Clinical Pharmacology
• Clinical Studies
  • STUDY 1
  • STUDY 2
• PYtest Indications and Usage
• Contraindications
• Warnings
• Precautions
  • General
  • Limitations of the Test
  • Radioactivity
  • Information for Patients
  • Carcinogenesis, mutagenesis, impairment of fertility
  • Drug Interactions
  • Pregnancy
  • Nursing mothers
  • Pediatric Use
• Side Effects
• Overdosage
• Dosage and Administration
  • Materials provided
  • Materials Needed but not Provided
  • Dosage
  • Procedural Notes
  • Step by Step Procedure for Balloon
  • Quality Control
  • Results
  • Expected Values
• How Supplied
• PRINCIPAL DISPLAY PANEL - PYtest* Kit Label

FULL PRESCRIBING INFORMATION

Description

PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (¹⁴C-Urea Breath Test) is a qualitative and non-invasive method for the diagnosis of Helicobacter pylori (H.pylori). To detect H.pylori, ¹⁴C-urea supplied in a capsule is swallowed by the patient. If gastric urease from H.pylori is present, Urea is split to form CO₂ and NH₃. Ten minutes after the patient ingests the capsule, a breath sample is collected into a balloon. The breath sample is later transferred to collection fluid to trap the labeled CO₂. The liquid sample is then analyzed in a liquid scintillation counter.

The PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Kit (¹⁴C-Urea Breath Test) is designed for use with the PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. capsule, a gelatin capsule for oral administration containing 1 µCi of ¹⁴C labeled urea. The urea is adsorbed on sugar spheres and colored yellow with fluorescein.

Data on C-urea

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

Radiation emission: beta-emission, 49 keV_mean, 156 keV_max, 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

Clinical Pharmacology

The urease enzyme is not present in mammalian cells, so the presence of urease in the stomach is evidence that bacteria are present. The presence of urease is not specific for H.pylori, but other bacteria are not usually found in the stomach. The principle of the breath test is shown in Figure 1.

Figure 1: Principle of Breath Test

To detect H.pylori, urea labeled with ¹⁴C is swallowed by the patient. If gastric urease from H.pylori is present, urea is split to form CO₂ and NH₃ at the interface between the gastric epithelium and lumen and ¹⁴CO₂ is absorbed into the blood and exhaled in the breath.

Following ingestion of the capsule by a patient with H.pylori, ¹⁴CO₂ excretion in the breath peaks between 10 and 15 minutes and declines thereafter with a biological half-life of about 15 minutes. ¹⁴C-urea that is not hydrolyzed by H.pylori is excreted in the urine with a half-life of approximately 12 hours. About 10% of the ¹⁴C remains in the body at 72 hours and is gradually excreted with a biological half-life of 40 days.

Clinical Studies

Two studies were performed. In both studies, patients with gastrointestinal symptoms underwent the breath test and an endoscopy. During the endoscopy, biopsy samples were taken from the antral gastric mucosa for histological analysis (2 samples, Giemsa stain) and rapid urease test (1 sample, CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.). Breath samples were mailed to the TRI-MED lab where they were read in a liquid scintillation counter.

Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. A breath sample DPM <50 was defined as a negative result. DPM ≥200 was defined as a positive result. DPM in the range of 50 -199 was classified as indeterminate.

STUDY 1

Of 186 patients who had histopathology and CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (80 men, 106 women), 53 were infected with H.pylori as determined by agreement between histology and CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.. The study results are summarized below:

Table 1: Study #1 (n=186, Indeterminate results included)

Histology and CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.
	H.pylori	Positive	Negative	Total
Notes: PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.
ppv = positive predictive value (true positive divided by total           PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. positive)
npv = negative predictive value (true negative divided by total           PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. negative)
PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.	Positive	51	8	59	ppv. 86%
(DPM	Indeterminate	1	8	9
10m.)	Negative	1	117	118	npv. 99%
	Total	53	133	186
		sensitivity 96%	specificity 88%

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 CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. were evaluated. The results are summarized below:

Table 2: Study #2 (n=76, Indeterminate results included)

Histology and CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.
	H.pylori	Positive	Negative	Total
Notes: PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.
ppv = positive predictive value (true positive divided by total           PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. positive)
npv = negative predictive value (true negative divided by total          PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. negative)
PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.	Positive	22	0	22	ppv. 100%
(DPM	Indeterminate	4	2	6
10m.)	Negative	1	47	48	npv. 98%
	Total	27	49	76
		sensitivity 82%	specificity 96%

PYtest Indications and Usage

PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (¹⁴C-Urea Breath Test) is indicated for use in the detection of gastric urease as an aid in the diagnosis of H.pylori infection in the human stomach. The test utilizes a liquid scintillation counter for the measurement of ¹⁴CO₂ in breath samples.

Contraindications

None

Warnings

None

Precautions

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 of H.pylori infection. If clinical signs and patient history suggest H.pylori infection, repeat the PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. 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 ¹⁴CO₂ concentration 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 PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (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

Pregnancy category C

Animal reproduction studies have not been conducted with PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. (¹⁴C-urea). It is also not known whether PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. should be given to a pregnant woman only if clearly needed.

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 PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. is administered to a nursing woman.

Pediatric Use

Clinical studies in children have not been conducted. However, PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. 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.

Side Effects

No adverse reactions were reported in clinical trials.

Overdosage

Risk from radiation is negligible even with a 1000 capsule overdose (0.3 rem). If overdose occurs, the patient may drink one glass of water (150 mL) every hour to hasten excretion of the isotope. Maximum excretion of Urea is achieved at a urine output of ≥2.0 mL/min.

Dosage and Administration

Materials provided

As shown in Figure 2, the PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Kit contains:

• PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. capsule
• Two 30 mL disposable cups
• One drinking straw
• One mylar collection balloon
• One report form
• One mailing box with labels The kit includes analysis by Kimberly-Clark of one balloon from one patient at one time point.

Figure 2: PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Kit

Materials Needed but not Provided

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

Dosage

One PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. 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 CO₂ varies 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 PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. or 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 PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc..

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

Table 4: Factors which might cause sub-optimal breath test results

Factor	Result	Comment
Recent antibiotic or bismuth (Pepto-Bismol, etc.)	false neg.	Relapse of partially treated Hp may take 1-4 weeks.
Omeprazole (or other proton pump inhibitors)	false neg.	These agents suppress Hp in 40% of patients. Discontinue for at least 2 weeks before performing the PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc..
Resective gastric surgery	false neg.	Isotope may empty rapidly from the stomach.
Resective gastric surgery	false pos.	Patient may be achlorhydric and have bacterial overgrowth (non-Hp urease).
Food in stomach (also bezoar, gastroparesis)	unknown	Isotope may not come into contact with gastric mucosa. Patient may be achlorhydric and/or have bacterial overgrowth (non-Hp urease).

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 PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc..

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 CLOtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.

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

How Supplied

PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Kit (¹⁴C-Urea Breath Test) is supplied as a kit containing a PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Capsule, a clear gelatin capsule containing 1µCi of ¹⁴C-urea and breath collection equipment.

PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Capsules are also supplied separately in unit dose packages of 1,10 and 100.

The PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. Capsule has a shelf life of two years. The expiration date is printed on the capsule label.

PYtestRegistered Trademark or Trademark of Kimberly-Clark Worldwide, Inc. 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

Kimberly-Clark Distributed in the U.S. by Kimberly-Clark Global Sales, LLC,
Roswell, GA 30076 USA
In USA, please call 1-800-KCHELPS • www.kchealthcare.com
Kimberly-Clark, Roswell, GA 30076 USA
Kimberly-Clark N.V., Belgicastraat 13, 1930 Zaventem, Belgium
Sponsored in Australia by Kimberly-Clark Australia Pty Limited; 52 Alfred Street,
Milsons Point, NSW 2061 • 1-800-101-021
©2003 KCWW. All rights reserved.

14-63-136-0-00/70080910 12/07

PRINCIPAL DISPLAY PANEL - PYtest* Kit Label

Kimberly-Clark* PYtest* Kit

¹⁴C-Urea Breath Test
for the detection of Helicobacter pylori

Contents - 10 PYtest* Capsules
PYtest* Breath Collection Accessories

For Dosage Information, Please See Package Insert
1 PYtest* capsule contains 1 µCi ¹⁴C-Urea
¹⁴C-Urea (5730years1/2, 156keV_[max] β-emission)

For In Vitro Diagnostic Use
Rx only
Store at 15°- 30°C (59°- 86°F)

*Registered Trademark or Trademark of Kimberly-Clark Worldwide, Inc.
©2003 KCWW. All rights reserved. 20-63-141-0-00/70080967