Half-life of GATTEX in patients with SBS1,2
~1.3 HOURS
(AGE: >17 YEARS)
GATTEX Mechanism of Action
How GATTEX works
Half-life of naturally occurring GLP-2 is ~7 minutes1,2
The amino acid sequence of naturally occurring GLP-2 and GATTEX are nearly identical, except for a single amino acid substitution—alanine replaced with glycine.1-4
GLP-2=glucagon-like peptide-2
GATTEX (teduglutide) enhanced intestinal absorption in adult patients with short bowel syndrome (SBS)1,3
Increased
Villus Height
Increased
Crypt Depth
Not an actual biopsy. Image is for illustrative purposes only and does not represent results from the study.
GATTEX enhanced gastrointestinal fluid (wet weight) absorption in adults by approximately 750–1000 mL/day1
The ability of GATTEX to improve intestinal absorption in children has not been investigated.
The ability of GATTEX (teduglutide) to improve intestinal absorption was studied in 17 adult subjects with SBS (n=2-3 per dose group) using daily doses of 0.03, 0.1, or 0.15 mg/kg (doses ranging from 0.6 to 3 times the recommended dose) in a 21-day, open-label, multicenter, dose-ranging study. Fourteen of 17 patients were dependent on parenteral support (PS). All subcutaneous (abdomen) doses studied, except 0.03 mg/kg once daily, resulted in enhanced gastrointestinal fluid (wet weight) absorption of approximately 750 to 1000 mL/day, and increased villus height and crypt depth of the intestinal mucosa.1
The recommended dosage of GATTEX for both adult and pediatric patients is 0.05 mg/kg once daily by subcutaneous injection. The recommended dosage in adult and pediatric patients with moderate and severe renal impairment and end-stage renal disease (estimated glomerular filtration rate [eGFR] <60 mL /min/1.73 m2) is 0.025 mg /kg once daily.1
Understanding the GATTEX
Mechanism of Action
Share the video below with your patients to see how GATTEX works.
“My surgeon had heard about GATTEX, and he explained that this drug might help me reduce the amount of volume and days on total parenteral nutrition (TPN).”
Patient Baseline Characteristics in STEPS1,5,7
| Average | Range | |
|---|---|---|
| Age | 50 years | 18-82 years |
| Estimated small bowel length |
77.3 cm | 5-343 cm |
| Length of time on PS | 6 years | 1-26 years |
| Prescribed days per week on PS |
5.73 days | 3-7 days |
| Infusion volume | 13 L/week | 0.9-35 L/week |
Intestinal Resection Baseline Characteristics1,7
Patients had varying types of intestinal resection1,7
-
44% (37/85) of patients did not have colon in continuity
— An average of 37% of the colons in these patients had been removed - 54% (13/24) of patients with an intact distal/terminal ileum had an ileocecal valve
- Stoma (most commonly jejunostomy and ileostomy) was present in 45% (38/85) of patients
The most common reasons for intestinal resection included1:
- Vascular disease: 34% (29/85)
- Crohn’s disease: 21% (18/85)
- Other: 21% (18/85)
See how to get your appropriate patients started, or keep reading to explore results with GATTEX, safety profile, dosing, time to response, and weaning PS.
Adult patients achieved significant reductions in parenteral support (PS) volume with GATTEX1*
2X more patients treated with GATTEX achieved ≥20% reduction in weekly PS volume vs placebo
At 6 months in STEPS study:
After 30 months, even more patients treated with GATTEX saw the same reduction
Who completed 30 months in STEPS and STEPS-2 studies:
93%
(28/30)
of patients treated with GATTEX achieved ≥20% reduction in weekly PS volume
*The primary endpoint in STEPS was defined as a patient achieving a ≥20% reduction in weekly PS volume from baseline (immediately before randomization) to Weeks 20 and 24. Clinical response in STEPS-2 was defined as a ≥20% reduction in weekly PS volume from baseline (start of GATTEX treatment) to the last visit.1,6
GATTEX (teduglutide) reduced average weekly parenteral support (PS) volume over time5,6
Average weekly PS volume reduction
STEPS: At 6 months (P<0.001)1§
Patients who received GATTEX achieved an average reduction of 4.4 L/week.¶
Patients who received placebo achieved an average reduction of 2.3 L/week.‖
STEPS + STEPS-2: Who completed 30 months5,6
After 30 months, patients treated with GATTEX (n=30) achieved a mean reduction in PS volume of 7.55 L/week, which represented a 66% reduction from baseline.
-66%
66% reduction in PS volume after 30 months of treatment with GATTEX1
§In STEPS, mean reduction in PS volume was a selected secondary endpoint.
¶From a pretreatment baseline of 12.9 L/week (n=43).
‖From a pretreatment baseline of 13.2 L/week (n=43).
“With the help of GATTEX, my doctor was able to cut my weekly PS. I'm now infusing fewer liters of PS a week.”
1 out of 3 adult patients achieved complete freedom from parenteral support (PS)1
Percentage of patients who achieved complete freedom from PS
Who completed 30 months in STEPS and STEPS-2 studies††:
33%
(10/30)
of patients treated with GATTEX weaned off PS completely
Of the 10 patients who achieved complete freedom from PS6:
3 of 10
- Had resection due to inflammatory bowel disease
- Did not have colon-in-continuity
7 of 10
- Had resection due to vascular and other causes
- Had colon-in-continuity
- The average duration of treatment to achieve complete freedom from PS was ~20 months (range: ~7 to ~30 months)7
- No patients completely weaned off of PS in STEPS
- Not all patients treated with GATTEX will fully wean off of PS or experience weekly PS volume reduction
††During the study, patients were maintained on GATTEX after weaning off of PS. Prior to GATTEX, these 10 patients required 3.5-13.4 L/week of PS for 1.2-15.5 years.
“Now, I spend my days off PS engaged in pastimes like being with friends, traveling, and engaging in volunteer activities.”
How long does it take GATTEX to work?
Time to response for adults on GATTEX may vary
Bowel anatomy may impact time to response
Post hoc analysis8
A Takeda-sponsored post hoc analysis of STEPS and STEPS-2 identified factors that may be associated with mean time to sustain parenteral support (PS) reduction.
To evaluate factors associated with sustained PS volume reduction and early vs late response, a Takeda-sponsored post hoc analysis was conducted of patients with SBS who were treated with GATTEX in the STEPS study (n=43) and who then continued treatment with GATTEX for up to 24 months in the extension study, STEPS-2.¶¶¶
Early responders (n=27)
3.6
Months(1.1 SD)
- Lower percentage had colon in continuity (51.9%)
- Patients had a lower mean percentage of colon remaining (24.6%)
- Fewer patients had an ileocecal valve (0%)
Late responders (n=7)
10.0
Months(6.1 SD)
- Higher percentage had colon in continuity (100%)
- Patients had a higher mean percentage of colon remaining (57.1%)
- More patients had an ileocecal valve (28.6%)
Early responders
- Patients who completed STEPS with a PS volume reduction of ≥20% from baseline at both Week-20 and Week-24 visits during STEPS
Late responders
- Patients who completed STEPS-2
- Patients who had a PS volume reduction of ≥20% from baseline at any 2 consecutive visits during the extension study or at both the Week-24 visit in STEPS and the Month-1 visit in STEPS-2
- PS volume reduction was defined as 2 consecutive visits with a PS volume reduction of ≥20%
- Time to sustained PS volume reduction was defined as the period between the baseline visit for STEPS and the second consecutive visit at which PS volume reduction was ≥20%
- A Kaplan-Meier analysis was conducted for time to sustained PS volume reduction; a multivariable Cox proportional hazards model was used for predictors of sustained PS volume reduction. Time to sustained PS volume reduction was described for early and late responders. Patient characteristics were described and compared between early vs late responders using chi-square tests for categorical variables and Wilcoxon rank sum tests for continuous variables.
Study limitations: This study was limited by the relatively small sample size, which may not have sufficient statistical power to identify factors associated with response. This study was also limited by the heterogeneity within the group of patients who had SBS with intestinal failure. The population consisted of patients who were subject to specific inclusion and exclusion criteria. Thus, the results may have limited generalizability.
Characteristics of early vs late responders8
| CHARACTERISTICS | EARLY RESPONDERS (n-27) |
LATE RESPONDERS (n=7) |
P VALUE |
|---|---|---|---|
| Baseline demographics | |||
| Age (years), mean (SD) | 51.6 (13.3) | 52.4 (10.2) | 0.966 |
| Male, n (%) | 14 (51.9) | 3 (42.9) | 0.672 |
| White, n (%) | 26 (96.3) | 7 (100.0) | 0.605 |
| BMI (kg/m2), mean (SD) | 22.3 (3.3) | 22.3 (3.9) | 0.881 |
| Baseline PS characteristics, mean (SD) | |||
| Composite fluid balance (L/week) | 17.3 (11.7) | 18.3 (15.0) | 0.966 |
| Actual baseline PS volume (L/week) | 13.5 (7.7) | 12.7 (9.8) | 0.639 |
| Time since start on PS dependence (years) | 7.4 (6.4) | 3.5 (3.0) | 0.287 |
| Actual number of days of PS per week | 5.8 (1.5) | 5.4 (1.8) | 0.537 |
| Concomitant medications | |||
| Narcotics, n (%) | 10 (37.0) | 3 (42.9) | 1.000 |
| Baseline SBS characteristics | |||
| Cause of major intestinal resection, n (%) | |||
| Crohn's disease | 7 (25.9) | 1 (14.3) | 1.000 |
| Vascular disease | 8 (29.6) | 4 (57.1) | 0.211 |
| Injury | 2 (7.4) | 1 (14.3) | 0.511 |
| Volvulus | 3 (11.1) | - | 1.000 |
| Cancer | 1 (3.7) | - | 1.000 |
| Other | 6 (22.2) | 1 (14.3) | 1.000 |
| Presence of stoma, n (%) | 15 (55.6) | 2 (28.6) | 0.203 |
| Type of stoma, n (%) | |||
| Jejunostomy | 10 (37.0) | - | 0.078 |
| Ileostomy | 3 (11.1) | - | 1.000 |
| Colostomy | 2 (7.4) | 2 (28.6) | 0.180 |
| Missing or not available | 12 (44.4) | 5 (71.4) | 0.398 |
| Colon-in-continuity, n (%) | 14 (51.9) | 7 (100.0) | 0.020‖‖‖ |
| Percentage of colon remaining, mean (SD) | 24.6 (26.1) | 57.1 (19.8) | 0.016‖‖‖ |
| Estimated remaining small intestine length (cm), n (%) | |||
| <60 cm | 11 (40.7) | 3 (42.9) | 1.000 |
| ≥60 cm | 14 (51.9) | 3 (42.9) | 1.000 |
| Missing | 2 (7.4) | 1 (14.3) | 0.511 |
| Presence of distal/terminal ileum, n (%) | 5 (18.5) | 3 (42.9) | 0.176 |
| Presence of ileocecal valve, n (%) | 0 (0.0) | 2 (28.6) | 0.004‖‖‖ |
| Time since last small bowel resection (years), mean (SD) | 5.8 (5.1) | 3.9 (2.7) | 0.639 |
Adapted from Joly et al, 2016, United European Gastroenterology Week.
¶¶¶This is a post hoc analysis of patients who completed STEPS and STEPS-2. Please note that efficacy in STEPS was based on the intent-to-treat population, while efficacy in STEPS-2 was based on study completers. Further randomized, controlled clinical studies are necessary to corroborate these findings.8-10
‖‖‖P<0.05.
Monitoring Timeline for adult patients receiving GATTEX
Within 6 months prior to starting GATTEX treatment1:
- Perform a colonoscopy of the entire colon with removal of polyps1
- Obtain baseline laboratory assessments (bilirubin, alkaline phosphatase, lipase, and amylase)1
| Ongoing | Every 6 months |
After 1 year of GATTEX* |
At least every 5 years |
||
|---|---|---|---|---|---|
| Colonoscopy1 | Examination of the entire colon with removal of polyps |
|
|
||
|
Laboratory assessments1 |
Bilirubin |
|
|||
| Alkaline phosphatase |
|
||||
| Lipase |
|
||||
| Amylase |
|
||||
| Clinical evaluations1 | Signs and symptoms of intestinal obstruction |
|
|||
| Signs and symptoms of fluid imbalance and fluid overload |
|
||||
| Increased absorption of concomitant oral medication(s) |
|
||||
| Observation of other adverse events |
|
| Colonoscopy after 1 year of GATTEX* and at least every 5 years1 |
|---|
| Examination of the entire colon with removal of polyps |
| Laboratory assessments every 6 months1 |
| Bilirubin |
| Alkaline phosphatase |
| Lipase |
| Amylase |
| Ongoing clinical evaluations1 |
| Signs and symptoms of intestinal obstruction |
| Signs and symptoms of fluid imbalance and fluid overload |
| Increased absorption of concomitant oral medication(s) |
| Observation of other adverse events |
Discontinuation of treatment with GATTEX may result in fluid and electrolyte imbalance. Fluid and electrolyte status should be monitored in patients who discontinue treatment with GATTEX.1
*Follow-up colonoscopy (or alternate imaging) is recommended at the end of 1 year of treatment with GATTEX.1
See how to get your appropriate patients started, or keep reading for information on dosing.
“Over time with GATTEX, my doctors started slowly reducing my PS. A year later, my PS had been stopped altogether.”
Weaning parenteral support (PS) while on GATTEX
Once you have decided GATTEX is appropriate for your patient with SBS, it's important to understand the weaning process. Below you will find information on weaning parenteral support (PS), which ranges from IV hydration to total parenteral nutrition (TPN), for patients with SBS. Not every patient will be able to wean completely off of PS. However, reducing the volume or number of days on PS may help patients reach their treatment goals.1
PS is lifesaving for patients with SBS9
When patients achieve and maintain nutrition/hydration goals with an optimal amount of PS (in conjunction with diet and antidiarrheals), there may be some hesitation to change therapy. However, once patients are optimized and stabilized on their individualized plan, they should begin reducing their dependence on PS.9,10
Weaning parenteral support (PS) is a multistep process9,10
Preparation
- Establish treatment goals for PS reductions, symptom management, and diet/lifestyle modifications
- Educate patients about their condition and why it’s important to reduce or eliminate PS
- Inform patients on the importance of their diet, signs of dehydration, and how oral rehydration solutions (ORS) can help
- Identify and coordinate with a multidisciplinary team (MDT)
Optimization
- Monitor hydration and nutrition status when adjusting PS and oral fluid intake
- Optimize medications used to treat SBS symptoms (ie, antidiarrheal, antisecretory, and pain management)
- Customize diet and use of ORS according to patient characteristics
PS modification and patient monitoring
- Once patient is optimized, begin reduction of PS volume or frequency (hours or days off)
- Monitor hydration and nutrition status at regular intervals
- Adjust medications for SBS symptoms if needed
- Monitor for electrolyte, nutrient, and vitamin deficiencies, as well as renal function
- Ensure the patient is increasing oral fluid intake with ORS
Ongoing monitoring
- Continue to monitor electrolytes as well as mineral and vitamin supplements at regular intervals, as needed
- Monitor renal function
- Reassess and establish new goals, as needed
- Observe patient compliance with diet, ORS, and supplements
- Monitor weight
Prepare a personalized parenteral support (PS) weaning plan with your patients
Develop the weaning plan based on patient characteristics as well as patients’ treatment goals10
Patients with short bowel syndrome (SBS) differ in age and pathophysiology as well as in duration of parenteral support (PS) and nutritional status. These and other factors can impact weaning success.9,11
Patient characteristics that can positively impact a PS weaning plan9,12
Characteristic
Influence on weaning success
Length of
remnant bowel Length of remnant bowel is important and can increase chances of weaning success but ultimately function of bowel is the primary factor
remnant bowel Length of remnant bowel is important and can increase chances of weaning success but ultimately function of bowel is the primary factor
Presence of a colon
Allows PS weaning by facilitating fluid and energy absorption
Presence of ileum/ileocecal valve
Slows small bowel transit time and may reduce reflux of colonic bacteria into the small intestine
Sufficient bowel adaptation
Increases absorption and extends intestinal transit time
Absence of underlying pathology/
disease Patients free of underlying conditions (i.e. Crohn’s disease, radiation enteritis, carcinoma) generally experience more complete PS weaning
disease Patients free of underlying conditions (i.e. Crohn’s disease, radiation enteritis, carcinoma) generally experience more complete PS weaning
Compliance
Patient compliance with all therapies (diet, oral rehydration solutions [ORS], antidiarrheal, other medications) can impact weaning success
Include a multidisciplinary team in the
parenteral support (PS) weaning plan
A multidisciplinary team (MDT) can help
ensure a successful weaning process10,13,14
Multidisciplinary care improves outcomes in weaning parenteral support (PS), facilitating enteral autonomy, and reducing complications. To establish an MDT, the first step is to start with a single dedicated physician who will drive the development of the team. This physician will connect with specialists needed to help support the patient. The size of the team may vary, depending on the circumstances. Start by adding a few specialists at a time who can contribute to the success of the patient’s weaning goals.10,13-15
Leading physician*
Assembles team and oversees treatment
strategy
Consulting physicians
(e.g. gastroenterologist (GI), surgeon,
nephrologist, infectious disease doctor)
Home care company
Provides infusion support
Pharmacist
Collaborates with care team on medications
and PS
Specialty pharmacy
Provides PS and GATTEX
Dietitian
Monitors nutrition and hydration
Nurse (PS/Ostomy)
Helps educate patients on PS infusions
and stoma care
Primary care physician
Manages overall health and medical plan
Social worker
Assists patients with challenges and connects
them with the appropriate resources
*While a gastroenterologist is often the leading physician, other physicians could serve in this role as well.
A stepwise, personalized weaning plan should accommodate the patient’s unique needs9,10
Depending on patient characteristics, eliminating PS requirements may not be possible — but patients may still achieve meaningful reductions in parenteral support (PS)
volume and time, with fewer hours/days on PS9,10,16
Clearly defined care protocols should be established for situations such as dehydration or nutritional instability that may require IV fluids or vitamin/mineral/electrolyte supplements and diet adjustment
Patients should have a good understanding of who is part of their multidisciplinary team, their contact information, and how each of them will help during the weaning process10,13-15
Patients need to remain consistent with all therapies (modified diet, ORS, medications, vitamin/mineral/electrolyte supplements, and use of PS and adherence to PS reductions as directed)
Water is not recommended for most patients with SBS.17
Homemade Oral Rehydration Solution
1 quart of ready to drink Gatorade® G2 Low Calorie*
1/2 teaspoon salt
Directions: Add salt to ready to drink Gatorade G2 and shake well.
Note: Potassium levels in this recipe are well below the recommended amount for an ORS
*Gatorade® is a registered trademark of PepsiCo.
Optimization prepares the patient for successful parenteral support (PS) weaning
Optimizing hydration and nutrition prepares the patient for parenteral support (PS) reduction9,10
Patients should be nutritionally stable (ie, meet dry weight, steady calorie and protein intake from all sources) and well hydrated before they begin to wean PS. Therefore, it is recommended that steps be taken to optimize diet, oral fluid intake, and antidiarrheal/antisecretory/pain management medications before starting the weaning process to avoid dehydration and malnutrition.
- Daily fluid goal (targeting urine output >1 L/day) must be met to ensure adequate hydration
- Blood and urine samples can be used to evaluate hydration and nutrition
Other measures to consider when optimizing patients for PS weaning
- Daily caloric intake and weight should be steady before attempting PS weaning
- Patient should be clinically stable (ie, meet adequate electrolyte levels, fluid status and weight goal) before starting the weaning process
In the STEPS and STEPS-2 studies, PS/IV support was optimized and stabilized prior to randomization1
- For ≤8 weeks prior to randomization, investigators optimized the PN/IV volume of all patients
- Optimization was followed by a 4–8 week period of fluid stabilization
Parenteral support (PS) modifications and patient monitoring
In STEPS and STEPS-2 studies, once a patient was optimized and stable, parenteral support (PS) infusions were slowly reduced over time.5,6 Gradual reductions minimize the risk of dehydration and increase the likelihood of weaning success.10
Reductions in PS are often made in one of the following ways9,10:
- Total infusion volume per week
- Infusion volume per day
- Number of infusion days per week
- Number of infusion hours per day
STEPS and STEPS-2 relied on urine output, but alternative approaches are available9,15
Nutrition-focused physical assessment
Stool output
Oral intake
Electrolyte and micronutrient levels
Body weight
Evaluating weaning in terms of intake, output, and other clinical measures
The overall approach for weaning PS may consider9,10:
- A patient’s intake (oral, enteral and parenteral support)
- A patient’s outputs (stool, urine, ostomy, etc.)
- Regular body weight monitoring
- Hydration tracked through urine output
- Lab testing to confirm nutritional needs are met
Discussing the weaning PS process with your patients can help guide an appropriate approach
Monitoring hydration and nutritional stability during and after parenteral support (PS)
After your patient has achieved their PS weaning goal, long-term monitoring of hydration and nutrition status is recommended10
Monitor electrolytes, trace elements, vitamins and minerals
Antidiarrheal medications should be continued and adjusted based on stool volume (stoma), frequency and consistency
Monitor weight for nutritional status
Adequate energy and fluid intake and sustained hydration should be reinforced
at each visit9,10
Ongoing monitoring
Parameters monitored in STEPS study7,18
(Evaluated every 1-4 weeks)
- Glucose, BUN, creatinine, electrolytes, calcium, magnesium, phosphorous
- CBC with differential
- Total bilirubin, direct bilirubin, AP, AST, ALT
- PTT, PT, INR
- Triglyceride level
- Serum proteins (total protein and albumin)
- Cholesterol
- GGT
- LDH
- Complete urinalysis
Additional parameters to consider monitoring in clinical practice18
Included in ASPEN Consensus Recommendations for monitoring during parenteral nutrition
- Iron indices
- Zinc, selenium, manganese, copper, chromium
- Vitamin A, 25-OH vitamin D, vitamin E
- Vitamin B12 and folate
- Carnitine
- TSH
Fat-soluble vitamins and micronutrients
If a patient cannot maintain adequate hydration or nutrition status after full PS weaning, PS should be restarted
Eliminating PS requirements is the ultimate goal for all patients with SBS, however reducing the hours per day or days per week on PS can provide substantial benefits.16
More About Weaning PS
Initiate PS Weaning for your appropriate patients with this comprehensive guide
Hypothetical Patient Profiles
Meet Lisa and Sonia, 2 hypothetical SBS patients. Their symptoms, histories, and exams demonstrate how different adult SBS patients may present.
Lisa | 49 years
- Diagnosed with SBS at 43
- Started GATTEX at 44
- Underlying cause of SBS: Proctocolectomy due to progression of Crohn's disease
Sonia | 42 years
- Diagnosed with SBS at 39
- Started GATTEX at 41
- Underlying cause of SBS: complications due to bariatric surgery
History of illness
- Recent hospitalization for dehydration and weight loss (5 kg in month)
- Ongoing issues with weakness and fatigue associated with dehydration
- Most recent resection in 2016 (age 43)
- Started on parenteral support (PS) in 2016 after resection (IV nutrition and fluids)
- 220 cm of small intestine remaining (primarily proximal jejunum and distal ileum)
- Permanent stoma and no remnant colon or rectum
- Crohn’s disease diagnosed at age 22; currently in remission
- Proctocolectomy at age 28 resulted in an ileostomy
Lisa’s experience starting GATTEX
- At 1-month visit, patient experienced hematoma at injection site and abdominal pain
- At 2-month visit, patient observed signs of dehydration; HCP increased oral rehydration solution intake to 56 oz per day
- At 3-month visit, increased oral intake; increased weight to 49 kg
Lisa’s experience weaning with GATTEX
- At 3-month visit, HCP decided to maintain current PS
- At 6-month visit, reduced PS by 10% after evaluating 48-hour urine output*
- At 12-month visit, reduced PS further (by 15%) based on ongoing monitoring*
*Reductions followed by safety evaluation after 1 week, including 48-hour urine collection and clinical evaluation: signs and symptoms of dehydration, weight changes, review of recorded oral fluid intake, blood samples (hematocrit, creatinine, blood urea nitrogen), and urine sodium.
History of illness
- Fluid loss (~1.5L/day) through ostomy
- Poor intestinal adaptation prevented transition to oral feeding
- Severe hypoalbuminemia
- Micronutrient deficiencies in lipid soluble vitamins, iron, zinc, and magnesium
- Gastroenterologist diagnosed SBS in 2019 (age 39)
Sonia’s experience starting GATTEX
- At 1-month visit, patient experienced abdominal discomfort
- At 2-month visit, hematoma at injection site; dehydration; intermittent abdominal pain
Sonia’s experience weaning with GATTEX
- At 3-month visit, after 48-hour urine output, PS was reduced by 10%*
- At 6-month visit, PS was reduced by 20%*
- At 9-month visit, after monitoring and 48-hour urine output, decision was made to maintain PS at current level
- At 1-year visit, PS was reduced by 25%*
*Reductions followed by safety evaluation after 1 week, including 48-hour urine collection and clinical evaluation: signs and symptoms of dehydration, weight changes, review of recorded oral fluid intake, blood samples (hematocrit, creatinine, blood urea nitrogen), and urine sodium.
