**Enteryx^TM^ Procedure Kit for GERD**

##### INSTRUCTIONS FOR USE

**CAUTION:** Federal (USA) law restricts this device to sale,
distribution, and use by or on the order of a physician.

This device should be used only by physicians with a thorough
understanding and training in the use of endoscopic injection of
materials for treatment of esophageal disorders.

**SYMBOLS**

+--------------+-------------------------------------------------------+
| ![           | It is important to read the instructions for use with |
| ](media/imag | careful attention to cautions, notes and warnings     |
| e1.wmf){widt | prior to using this product.                          |
| h="0.2743055 |                                                       |
| 555555556in" |                                                       |
| height=      |                                                       |
| "0.240277777 |                                                       |
| 77777778in"} |                                                       |
+--------------+-------------------------------------------------------+
| ![           | STERILE: This device is provided sterile. Syringes,   |
| ](media/imag | needles and Enteryx™ injectors sterilized using       |
| e2.wmf){widt | ethylene oxide gas.                                   |
| h="0.7576388 |                                                       |
| 888888889in" |                                                       |
| height=      |                                                       |
| "0.18125in"} |                                                       |
+--------------+-------------------------------------------------------+
| ![](media    | STERILE: This device is provided sterile. Enteryx™    |
| /image3.wmf) | and Primer solutions sterilized using dry heat.       |
+--------------+-------------------------------------------------------+
| ![]          | DO NOT REUSE OR RESTERILIZE                           |
| (media/image |                                                       |
| 4.wmf){width |                                                       |
| ="0.25277777 |                                                       |
| 777777777in" |                                                       |
| height=      |                                                       |
| "0.252777777 |                                                       |
| 77777777in"} |                                                       |
+--------------+-------------------------------------------------------+
| ![](media/i  | Keep dry                                              |
| mage5.wmf){w |                                                       |
| idth="0.3in" |                                                       |
| height       |                                                       |
| ="0.29513888 |                                                       |
| 88888889in"} |                                                       |
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| ![](media/i  | Keep away from heat                                   |
| mage6.wmf){w |                                                       |
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| height=      |                                                       |
| "0.295833333 |                                                       |
| 33333334in"} |                                                       |
+--------------+-------------------------------------------------------+
| ####### REF  | Catalog Number                                        |
+--------------+-------------------------------------------------------+
| ![]          | Use by                                                |
| (media/image |                                                       |
| 7.wmf){width |                                                       |
| ="0.27569444 |                                                       |
| 444444446in" |                                                       |
| hei          |                                                       |
| ght="0.3in"} |                                                       |
+--------------+-------------------------------------------------------+
| ![](media/i  | Batch code                                            |
| mage8.wmf){w |                                                       |
| idth="0.5in" |                                                       |
| height=      |                                                       |
| "0.263194444 |                                                       |
| 44444445in"} |                                                       |
+--------------+-------------------------------------------------------+

#### 

#### DESCRIPTION

## Enteryx Procedure Kit is comprised of the following components:

[Enteryx Procedure Kit 900-100137]{.underline}

Enteryx solution (1) 10 ml 800-100180

Primer solution (1) 10 ml 800-100181

Enteryx Injector (1) 2.4 mmx165 cm 900-100000

Syringes (2) 1ml 900-100129

Needles (2) 18G x1 800-100186

#### INDICATIONS FOR USE

The Enteryx procedure kit is indicated for endoscopic injection into the
lower esophageal sphincter (LES) for the treatment for gastroesophageal
reflux disease (GERD).

#### CONTRAINDICATIONS

The Enteryx procedure is contraindicated in patients with portal
hypertension.

#### 

#### PRECAUTIONS

The safety and effectiveness have not been established in patients with
Barrett's epithelium, scleroderma, esophageal motility disorders,
esophageal or gastric cancer, large hiatal hernias ( 3cm by endoscopic
evaluation), prior gastric or GERD surgery, persistent high grade
esophagitis, esophageal or gastric varices, gross obesity (BMI 35), or
immune suppressant therapy. The safety and effectiveness have not been
established in pregnant or lactating women.

#### DIRECTIONS FOR USE

###### Patient Preparation

Prep patient as required for upper GI endoscopy. It is recommended that
patients be administered prophylactic antibiotics before and after
procedure.

###### Enteryx Procedure Preparation

1\. Resuspend the Enteryx solution by shaking for at least 10 minutes
prior to use.

2\. Remove the Enteryx injector from the pouch and carefully straighten
by uncoiling. Confirm that the needle fully deploys and retracts from
the distal end of the injector.

3.  Remove Primer solution from the vial with the syringe and needle
    supplied in the kit. Attach syringe to the Enteryx injector. With
    the needle fully deployed on the Enteryx injector, flush and prime
    the injector.

4.  Draw the Enteryx solution into the second syringe and needle, attach
    the syringe to the Enteryx injector and pre-load the system,
    completely filling the injector lumen removing all of the Primer
    solution and air.

5.  Refill the syringe with the Enteryx solution and attach to the
    Enteryx injector. The Enteryx injector is then ready to be passed
    into the working channel of the gastroscope.

**[Enteryx Injection Procedure]{.underline}**

1.  Introduce gastroscope and visualize the lower esophageal sphincter
    (LES), the squamo-columnar junction and the cardia of the stomach.

2.  Pass the Enteryx injector down the working channel of the
    gastroscope until the tip is visualized at the distal end.

3.  Place the tip of the Enteryx injector at the desired location at or
    just below the squamocolumnar junction. Deploy the injector needle,
    puncture the mucosa in an antegrade direction, and advance the
    needle into the muscle.

4.  Place at least 6ml of Enteryx solution circumferentially into and
    along the muscle layer of the lower esophageal sphincter. If the
    material forms an arc or ring, continue to use multiple syringes to
    add material at the same injection position. Otherwise use multiple
    discrete injections of 1-2 ml each for a total of at least 6ml of
    Enteryx solution circumferentially into and along the muscle layer
    of the lower esophageal sphincter.

5.  The injection rate should be [no faster than 1.0
    ml/minute]{.underline}. Slow injection speeds allow for consistent
    placement of the Enteryx solution within and along the muscle layer
    of the lower esophageal sphincter.

6.  Allow the needle to remain in place for at least 20 seconds to allow
    for stabilization of the Enteryx material.

**[Instructions to Patients]{.underline}**

1.  The majority of patients experience mild to moderate retrosternal
    pain following the procedure. It is recommended that patients take
    pain medication prophylactically.

2.  Patients may notice a garlic-type smell or taste after the
    procedure. This is normal and typically lasts no more than several
    days.

3.  It is recommended that patients eat only bland, non-spicy and soft
    foods for 5 days following the procedure.

4.  Patients should continue administration of their current
    anti-secretory medication(s) for approximately 10 days following
    treatment with Enteryx.

#### CLINICAL STUDIES

**Use of GERD Medications**

A successful outcome was defined as elimination of all PPI use or a
reduction in use of PPIs of at least 50% as compared to baseline usage.
Patients who experienced a smaller reduction in use of PPIs, i.e.,
\<50%, who continued to use PPIs at the baseline levels, or who required
an increase in PPI usage were considered not improved. []{.mark}

[]{.mark}

At twelve months, 80.3% of all study subjects (C.I. 69.9% to 88.3%) were
able to completely eliminate (70.4%) or reduce their use of PPIs by ≥50%
(9.9%). The low level utilization of supplementary non-PPI GERD
medications at 12 months was comparable to baseline use of these
medications while on PPIs, demonstrating that PPI therapy was not simply
being replaced with non-PPI treatment. Therefore it can be concluded
that treatment with Enteryx is highly effective in the management of
GERD, as evidenced by the ability of GERD patients with a history of use
of PPIs and other GERD medication to eliminate or significantly reduce
use of these medications.

**PPI Use 12 Months post-procedure**

+------------------------+---------------+----------------------------+
|                        | **N**         | **% (CI)** [^1]            |
+------------------------+---------------+----------------------------+
| **Medication           | 65/81         | 80.3% (69.9 to 88.3%)      |
| Improved**             |               |                            |
+------------------------+---------------+----------------------------+
| > Off all PPIs         | 57            | 70.4%                      |
+------------------------+---------------+----------------------------+
| > Dose reduced 50%     | 8             | 9.9%                       |
+------------------------+---------------+----------------------------+
|                        |               |                            |
+------------------------+---------------+----------------------------+
| **Medication Not       | 16/81         | 19.7%                      |
| Improved**             |               |                            |
+------------------------+---------------+----------------------------+
| > Dose reduced \< 50%  | 1             | 1.2%                       |
+------------------------+---------------+----------------------------+
| > Dose maintained      | 12            | 14.8%                      |
+------------------------+---------------+----------------------------+
| > Dose increased       | 3             | 3.7%                       |
+------------------------+---------------+----------------------------+

**other efficacy outcomes**

**GERD-Health Related Quality of Life (HRQL)**

### Results of administering the GERD-HRQL instrument to each study subject were reported as the sum of questions related to heartburn scores (sum of questions 1-9) and as the sum of questions related to regurgitation scores (sum of questions 10-13). 

### 

### Sum of Questions 1-9 (Heartburn Score)

> The mean severity score for the sum of questions 1-9 was significantly
> worse at baseline with patients off PPI therapy as compared to
> baseline on PPI medications (26.4 vs 5.4, p\<0.001). Mean severity
> score improved significantly following treatment with Enteryx as
> compared to baseline scores while off PPIs at each follow-up interval
> (p\<0.001). Consistent with the findings for each of the individual
> questions that are comprised in the summary score, scores following
> Enteryx treatment were comparable to those observed for patients on
> PPI therapy at baseline, further confirming that treatment with
> Enteryx is an effective alternative to chronic use of PPI therapy.

### Sum of Questions 10-13 (Regurgitation Score)

> The mean regurgitation severity score for the sum of questions 10-13
> was significantly worse at baseline with patients off PPI therapy as
> compared to baseline PPI medications (11.1 vs 2.8, p\<0.001). Mean
> severity scores following Enteryx treatment were significantly
> improved compared to baseline scores for patients off PPI treatment
> (p\<0.001). Also consistent with the scores for the individual
> questions, scores for the sum of questions 10-13 were comparable for
> patients at baseline while on PPIs and following treatment with
> Enteryx.
>
> In conclusion, the GERD-HRQL data indicate that at 12 months following
> Enteryx treatment, study subjects felt significantly better compared
> to baseline symptoms off PPIs and had comparable symptom control to
> baseline scores on PPIs. These data illustrate that the Enteryx
> procedure can relieve heartburn and regurgitation symptoms and provide
> an effective alternative to chronic PPI use.

**Baseline (on PPIs) Baseline (off PPIs)**

**Mean Mean**

**N (SD) N (SD) p value**

**Symptom score**

GERD-HRQL (Q1-9) 85 5.4 (3.74) 85 26.4 (6.62) \<0.001

GERD-HRQL (Q10-13) 85 2.8 (3.33) 85 11.1 (5.31) \<0.001

**Baseline (off PPIs) 12 Months post-Treatment Mean Mean**

**N (SD) N (SD) p value**

**Symptom score**

GERD-HRQL (Q1-9) 77 26.2 (6.67) 77 8.9 (9.70) \<0.001

GERD-HRQL (Q10-13) 77 10.9 (5.40) 77 3.1 (4.22) \<0.001

#### SF-36 Health Survey

The SF-36 Health Survey questionnaire, another secondary efficacy
measurement, was completed by each study subject at baseline while on
PPI treatment, at baseline following withdrawal of PPI treatment for
10-14 days, and at 1, 3, 6 and 12 months following treatment with
Enteryx. The questionnaire consists of a mental component score (MCS)
and a physical component score (PCS). SF-36 PCS mean scores at baseline
were better for subjects while on PPI therapy than off PPIs. At 12
months following treatment with Enteryx, mean physical component scores
were also significantly improved over the mean score at baseline for
subjects off PPI therapy (49.4 vs 43.4, p\<0.001) and were comparable to
scores reported at baseline for subjects while on PPIs.

SF-36 MCS mean scores were *not* significantly better for subjects while
on PPI therapy than off PPIs at baseline. At 12 months following
treatment with Enteryx, mean scores were not significantly different
than subjects either on PPI therapy at baseline (50.0 vs. 51.4, p=0.444)
or off PPIs at baseline (50.5 vs. 50.2, p=0.160). Since the change from
baseline for SF-36 MCS was not statistically significant by the Wilcoxon
signed ranks test, the results were examined for the patients who were
improved at 12 months (i.e., PPI use eliminated or reduced ≥ 50%) using
the sign test. While a less powerful statistical tool, patients whose
medication use improved following Enteryx treatment continued to have
statistical significance (p=.026), suggesting a favorable trend in
treatment responders.

Together, these findings suggest that Enteryx is capable of replacing
PPIs with no change in SF-36 scores.

Baseline (on PPIs) Baseline (off PPIs)

**Mean Mean**

**N (SD) N (SD) p value**

**Quality of life score**

SF-36 MCS 81 51.2 (9.44) 81 48.5 (11.49) 0.077

SF-36 PCS 81 47.8 (9.43) 81 43.1 (10.13) \<0.001

**Baseline (off PPIs) 12 Months post-Treatment**

**Mean Mean**

**N (SD) N (SD) p value**

**Quality of life score**

SF-36 MCS 74 50.2 (9.71) 74 50.5 (10.76) 0.160

SF-36 PCS 74 43.4 (10.16) 74 49.4 (9.32) \<0.001

**pH-Metry**

Subjects underwent prolonged (\> 12 hour) pH probe monitoring at
baseline after at least 10 days off PPI therapy. The study was repeated
again at six and twelve months following Enteryx treatment. The
following data were recorded:

-   \% total time pH [\<]{.underline} 4

-   \% upright time pH [\<]{.underline} 4

-   \% supine time pH [\<]{.underline} 4

-   total number of episodes

-   longest episode duration (minutes)

**Percentage of Total** **Time pH \< 4**

For all subjects with paired data at Month 12, 26/67 (39%) of subjects
normalized their pH measurement, as compared to baseline. Further, 43.1%
(25/58) of patients who experienced an improvement in PPI use at 12
months also had normalized pH. In contrast, among patients who did not
experience an improvement in PPI use at 12 months, only 11.1% (1/9) had
normalized pH.

At baseline for the cohort of patients who had baseline and 12 month pH
metry performed, the mean percentage of time during testing that pH was
\< 4 was 14.34% (SD 14.68%). At twelve months following Enteryx
treatment, the mean percentage of time at pH \< 4 was 9.21% (SD 9%). The
mean overall percentage of time at pH \< 4 was significantly reduced
(improved) at twelve months following Enteryx treatment (p = 0.002)
compared to baseline off PPIs. These statistically significant
reductions in overall time at pH \< 4 are indicative of a significant
improvement in pH-metry at six and twelve months post-treatment with
Enteryx.

**Percentage of Upright Time pH \< 4**

At baseline for the cohort of patients who had baseline and 12 month pH
metry performed, the mean percentage of upright time during testing that
pH was \< 4 was 14.27% (SD 15.35%). At twelve months following Enteryx
treatment, the mean percentage of upright time at pH \< 4 was 9.92% (SD
10.72%). The mean percentage upright time at pH \< 4 was significantly
reduced (improved) at twelve months following Enteryx treatment (p =
0.026) compared to baseline off PPIs. These statistically significant
reductions in upright time at pH\<4 are indicative of a significant
improvement in pH-metry at six and twelve months post-treatment with
Enteryx.

**Percentage of Supine Time pH \< 4**

At baseline for the cohort of patients who had baseline and 12 month pH
metry performed, the mean percentage of supine time during testing that
pH was \< 4 was 12.01% (SD 18.57%). At twelve months following Enteryx
treatment, the mean percentage supine time at pH \< 4 was 6.97% (SD
12.08%). The mean percentage supine time at pH \< 4 was significantly
reduced (improved) at twelve months following Enteryx treatment (p =
0.032) compared to baseline off PPIs. These statistically significant
reductions in supine time at pH\<4 are indicative of a significant
improvement in pH-metry at six and twelve months post-treatment with
Enteryx.

##### Total Number of Episodes 

##### 

At baseline for the cohort of patients who had baseline and 12 month
pH-metry performed, the mean total number of episodes with pH was \< 4
was 162.04 (SD 112.12). At twelve months following Enteryx treatment,
the mean total number of episodes with pH \< 4 was 114.82 (SD 77.21).
The mean total number of episodes with pH \< 4 was significantly reduced
(improved) at twelve months following Enteryx treatment (p = 0.002)
compared to baseline off PPIs. These statistically significant
reductions in the mean total number of episodes with pH\<4 are
indicative of a significant improvement in pH-metry at six and twelve
months post-treatment with Enteryx.

##### Longest Episode Duration

The longest recorded episode duration of pH \< 4 in study subjects at
baseline for the patients with baseline and 12 month data was 33.5
minutes (SD 45.89), while the longest recorded episode duration at 12
months follow-up after treatment with Enteryx, was 21.4 min. (SD 25.54).
These results indicate that there was a reduction in the maximum episode
duration at the twelve month visit following Enteryx treatment as
compared to baseline off PPI treatment, although this difference did not
reach statistical significance (p=0.209).

**Baseline (off PPIs) 12 Months**

**Mean Mean**

**N (SD) N (SD) p value**

**24-hr pH monitoring**

pH 4 (%) total 67 14.34 (14.68) 67 9.21 (9.00) 0.002

pH 4 (%) upright 58 14.27 (15.35) 58 9.92 (10.72) 0.026

pH 4 (%) supine 59 12.01 (18.57) 59 6.97 (12.08) 0.032

Number of episodes (Normalized to 24 hrs) 67 162.04 (112.12) 67 114.82
(77.21) 0.002

Longest episode (min) 65 33.5 (45.89) 65 21.4 (25.54) 0.209

MANOMETRY

Subjects underwent manometry before treatment with Enteryx (i.e., within
the three months prior to enrollment), six months, and twelve months
following Enteryx treatment. Lower esophageal sphincter (LES) pressure
and length were recorded, as was peristaltic amplitude and residual LES
pressure during relaxation.

There were no significant changes or findings following treatment with
Enteryx, with the exception of LES length. Mean LES length increased at
six months. While this increase was significant at six months as
compared to baseline, the LES length at 12 months was not statistically
different compared to baseline (2.8 vs. 2.6, p=0.258). Since the change
from baseline was not statistically significant by the Wilcoxon signed
ranks test, the results were examined for the patients who were improved
at 12 months (i.e., PPI use eliminated or reduced ≥ 50%) using the sign
test. While a less powerful statistical tool, patients whose medication
use improved following Enteryx treatment continued to have significantly
longer LES length (p = 0.012), suggesting a favorable trend in treatment
responders.

+--------------------------+--------------------+----------+-----------+
| **Physiologic Method**   |                    | **Ba     | **Month   |
|                          |                    | seline** | 12**      |
+--------------------------+--------------------+----------+-----------+
| **LES pressure**         | N                  | 69       | 69        |
|                          |                    |          |           |
| **(mm Hg)**              |                    |          |           |
+--------------------------+--------------------+----------+-----------+
|                          | Mean               | 14.27    | 13.10     |
+--------------------------+--------------------+----------+-----------+
|                          | Standard deviation | 7.03     | 7.75      |
+--------------------------+--------------------+----------+-----------+
|                          | p-value[^2]        |          | 0.651     |
+--------------------------+--------------------+----------+-----------+
| **LES length (cm)**      | N                  | 59       | 59        |
+--------------------------+--------------------+----------+-----------+
|                          | Mean               | 2.6      | 2.8       |
+--------------------------+--------------------+----------+-----------+
|                          | Standard deviation | 1.04     | 1.28      |
+--------------------------+--------------------+----------+-----------+
|                          | p-value            |          | 0.258     |
+--------------------------+--------------------+----------+-----------+
| **Peristaltic amplitude  | N                  | 68       | 68        |
| (mm Hg)**                |                    |          |           |
+--------------------------+--------------------+----------+-----------+
|                          | Mean               | 74.7     | 79.2      |
+--------------------------+--------------------+----------+-----------+
|                          | Standard deviation | 30.75    | 36.82     |
+--------------------------+--------------------+----------+-----------+
|                          | p-value            |          | 0.502     |
+--------------------------+--------------------+----------+-----------+
| **Residual LESP during   | N                  | 65       | 65        |
| relaxation (mm Hg)**     |                    |          |           |
+--------------------------+--------------------+----------+-----------+
|                          | Mean               | 2.90     | 2.53      |
+--------------------------+--------------------+----------+-----------+
|                          | Standard deviation | 5.39     | 3.84      |
+--------------------------+--------------------+----------+-----------+
|                          | p-value            |          | 0.577     |
+--------------------------+--------------------+----------+-----------+

**SAFETY RESULTS**

Adverse events were classified as device related, procedure related, and
unrelated to the device or procedure. The severity of adverse events was
defined as follows:

-   Mild: causing no limitation of usual activities

-   Moderate: causing some limitation of usual activities

-   Severe: causing inability to carry out usual activities.

This definition of "severe" adverse events was in contrast with the
description used in the majority of clinical trials. Customarily,
"severe" is used to describe adverse events that may be reportable under
21 CFR 812.150 if they are serious and device related, i.e., lead to
death, are potentially life threatening, cause disability or require or
prolong hospitalization. In this trial, due to the general good health
of the study participants, more conservative definitions were applied.
On this basis, "severe" events were defined in terms of disruption of
the patient's daily life. The classification of mild, moderate, or
severe was not related to whether medical intervention was necessary.

There were no serious adverse device related events reported during the
course of this trial, i.e., there were no events that were potentially
life threatening or required surgical intervention.

A total of 122 device-related adverse events were reported for the study
population. These adverse events included retrosternal chest pain (78/85
or 91.8%), dysphagia (17/85, or 20.0%), fever (10/85, or 11.8%),
belching/burping (6/85, or 7.1%), bloating/flatulence (5/85, or 5.9%),
body odor/bad taste (4/85, or 4.7%), and one case each of rib pain and
flu syndrome. Of these adverse events, only five (4%) events were rated
as severe at onset, which as noted above, indicated interference with
the subject's daily life. The "severe" device-related adverse events
consisted of retrosternal chest pain (n=4) and bloating (n=1).

> **Device-Related Adverse Events**
>
> **(85 Patients)**

+----------------------------------+-----+---------+-----+----+------+
| > **Event**                      | **  | **Mod   | *   | ** | *    |
|                                  | Mil | erate** | *Se | \# | *%** |
|                                  | d** |         | ver | ** |      |
|                                  |     |         | e** |    |      |
+----------------------------------+-----+---------+-----+----+------+
| > Retrosternal Chest Pain        | 39  | 35      | 4   | 78 | 9    |
|                                  |     |         |     |    | 1.8% |
+----------------------------------+-----+---------+-----+----+------+
| > Dysphagia                      | 10  | 7       | 0   | 17 | 2    |
|                                  |     |         |     |    | 0.0% |
+----------------------------------+-----+---------+-----+----+------+
| > Fever                          | 7   | 3       | 0   | 10 | 1    |
|                                  |     |         |     |    | 1.8% |
+----------------------------------+-----+---------+-----+----+------+
| > Belching/Burping               | 3   | 3       | 0   | 6  | 7.1% |
+----------------------------------+-----+---------+-----+----+------+
| > Bloating/Flatulence            | 1   | 3       | 1   | 5  | 5.9% |
+----------------------------------+-----+---------+-----+----+------+
| > Other                          |     |         |     |    |      |
+----------------------------------+-----+---------+-----+----+------+
| > Body Odor/Bad Taste            | 2   | 2       | 0   | 4  | 4.7% |
+----------------------------------+-----+---------+-----+----+------+
| > Rib Pain                       | 0   | 1       | 0   | 1  | 1.2% |
+----------------------------------+-----+---------+-----+----+------+
| > Flu Syndrome                   | 1   | 0       | 0   | 1  | 1.2% |
+----------------------------------+-----+---------+-----+----+------+

A total of 29 (34.1%) adverse events related to the procedure were
reported during the course of this study. None of these events were
considered to be severe. The events consisted of pharyngitis (n=9),
nausea and vomiting (n=7), nausea (n=5), shoulder pain (n=3), dry mouth
(n=2), anxiety (n=2), and breast pain (n=1).

**Severity of Procedure-Related Adverse Events**

(85 patients)

+----------------------------------+-----+---------+-----+----+------+
| > **Event**                      | **  | **Mod   | *   | ** | *    |
|                                  | Mil | erate** | *Se | \# | *%** |
|                                  | d** |         | ver | ** |      |
|                                  |     |         | e** |    |      |
+----------------------------------+-----+---------+-----+----+------+
| > Sore Throat (Pharyngitis)      | 8   | 1       | 0   | 9  | 1    |
|                                  |     |         |     |    | 0.6% |
+----------------------------------+-----+---------+-----+----+------+
| > Nausea / Vomiting              | 3   | 4       | 0   | 7  | 8.2% |
+----------------------------------+-----+---------+-----+----+------+
| > Nausea                         | 3   | 2       | 0   | 5  | 5.9% |
+----------------------------------+-----+---------+-----+----+------+
| > Other                          |     |         |     |    |      |
+----------------------------------+-----+---------+-----+----+------+
| > Shoulder Pain                  | 1   | 2       | 0   | 3  | 3.5% |
+----------------------------------+-----+---------+-----+----+------+
| > Dry mouth                      | 1   | 1       | 0   | 2  | 2.4% |
+----------------------------------+-----+---------+-----+----+------+
| > Anxiety                        | 1   | 1       | 0   | 2  | 2.4% |
+----------------------------------+-----+---------+-----+----+------+
| > Breast Pain                    | 0   | 1       | 0   | 1  | 1.2% |
+----------------------------------+-----+---------+-----+----+------+

The procedure related adverse events were anticipated and consistent
with what is generally expected during the course of therapeutic
endoscopy procedure.

(85 Patients)

  ----------------------------------- ----------- ----------- ----------- ----------- -----------
                                                                                      

                                                                                      

                                                                                      

                                                                                      

                                                                                      

                                                                                      

                                      []{.mark}   []{.mark}   []{.mark}   []{.mark}   []{.mark}

                                                                                      

                                                                                      

                                                                                      
  ----------------------------------- ----------- ----------- ----------- ----------- -----------

(85 patients)

  ----------------------------------- ----------- ----------- ----------- ----------- -----------
                                                                                      

                                                                                      

                                                                                      

                                                                                      

                                      []{.mark}   []{.mark}   []{.mark}   []{.mark}   []{.mark}

                                                                                      

                                                                                      

                                                                                      

                                                                                      
  ----------------------------------- ----------- ----------- ----------- ----------- -----------

[]{.mark}

[The procedure related adverse events were anticipated and consistent
with what is generally expected during the course of therapeutic
endoscopy procedure.]{.mark}

**PROCEDURAL PRECAUTIONS**

Use only the supplied syringe, needle and Enteryx injector to inject the
DMSO based Primer and Enteryx solutions. Other syringes, needles and
injectors may not be compatible. All gastroscopes manufactured by
Olympus before 2001 have been found to be DMSO compatible. The user
should verify the chemical compatibility of other gastroscopes.

Failure to continuously mix Enteryx solution for the required time may
result in inadequate suspension of the tantalum contrast agent,
resulting in reduced fluoroscopic visualization.

Premature precipitation of the Enteryx solution may occur if the liquid
comes in contact with saline, blood, or mucosal fluid.

Inspect all vials and pouches for damage prior to use. If damage is
suspected, discard item and replace.

If flow through the injector becomes restricted, do not attempt to clear
the injector by high-pressure infusion. Use of excessive pressure may
result in injector rupture. Remove the injector and replace it with a
new one. Flush with the Primer solution prior to use.

Failure to uncoil the Enteryx injector prior to deploying and retracting
the needle may cause injector damage. If injector is damaged, discard
and replace.

Inject the Enteryx and Primer solutions at a slow, steady rate but not
greater than 1ml/minute as described in step 5 of the injection
procedure. Faster injection speeds may result in inconsistent placement
of the Enteryx solution.

Use the Enteryx and Primer solutions at or above 65F (19C). If product
freezes due to exposure to colder temperatures, thaw at room temperature
before use.

+-----------------------+------------------------+---------------------+
| **[Manufa             | ###### Authorize       | **[International    |
| cturer]{.underline}** | d Representative in EU | Distribu            |
|                       |                        | tor]{.underline}**\ |
| Enteric Medical       | OPUS MEDICAL bvba.     | Boston Scientific   |
| Technologies, Inc.    |                        | Corporation         |
|                       | Spoorwegstraat 76      |                     |
| 551 Foster City       |                        | One Boston          |
| Blvd., Suite G        | B-3500 Hasselt Belgium | Scientific Place    |
|                       |                        |                     |
| Foster City, CA       |                        | Natick, MA 01760    |
| 94404, USA            |                        |                     |
+-----------------------+------------------------+---------------------+
|                       |                        |                     |
+-----------------------+------------------------+---------------------+

Olympus is a registered trademark of Olympus Optical Co., Ltd.

2001 Copyright Enteric Medical Technologies. All Rights Reserved.

[^1]: Clopper-Pearson 95% Confidence Interval

[^2]: Wilcoxon Signed-Rank