The colon-cleansing efficacy and safety of monobasic sodium phosphate and dibasic sodium phosphate tablets was evaluated in 2 randomized, investigator-blinded, actively-controlled, multi center, U.S. trials in patients scheduled to have an elective colonoscopy. The trials consisted of a dose ranging and a confirmatory phase 3 study.

In the phase 3 trial, patients were randomized into one of the following three sodium phosphate treatment groups: 1) Visicol containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with at least 3.6 quarts of clear liquids; 2) monobasic sodium phosphate and dibasic sodium phosphate tablets containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with 2.5 quarts of clear liquids; and 3) Monobasic sodium phosphate and dibasic sodium phosphate tablets containing 48 grams of sodium phosphate (30 grams in the evening before the colonoscopy and 18 grams on the next day) with 2 quarts of clear liquids. Patients were instructed to eat a light breakfast before noon on the day prior to the colonoscopy and then were told to drink only clear liquids after noon on the day prior to the colonoscopy.

The primary efficacy endpoint was the overall colon cleansing response rate in the 4-point Colonic Contents Scale. Response was defined as a rating of “excellent” or “good” on the 4-point scale as determined by the blinded colonoscopist. This phase 3 study was planned to assess the non-inferiority of the two monobasic sodium phosphate and dibasic sodium phosphate tablets groups compared to the Visicol group.

    

The efficacy analysis included 704 adult patients who had an elective colonoscopy. Patients ranged in age from 21 to 89 years old (mean age 56 years old) with 55% female and 45% male patients. Race was distributed as follows: 87% Caucasian, 10% African American, and 3% other race. The monobasic sodium phosphate and dibasic sodium phosphate tablets 60 gram and 48 gram treatment groups demonstrated non-inferiority compared to Visicol. See Table 1 for the results.

1Colon-cleansing efficacy was based on response rate to treatment. A patient was considered to be a responder if overall colon cleansing was rated as “excellent” or “good” on a 4-point scale based on the amount of retained “colonic contents”. Excellent was defined as >90% of mucosa seen, mostly liquid stool, minimal suctioning need for adequate visualization. Good was defined as >90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization. Fair was defined as >90% of mucosa seen, mixture of liquid and semisolid stool, could be suctioned and/or washed. Inadequate was defined as <90% of mucosa seen, mixture of semisolid and/or solid stool which could not be suctioned or washed.

2On the day of the colonoscopy, study medication was taken 3 to 5 hours before the start of the colonoscopy.

Electrolyte Changes

In the monobasic sodium phosphate and dibasic sodium phosphate tablets clinical studies, expected serum electrolyte changes (including phosphate, calcium, potassium, and sodium levels) have been observed in patients taking monobasic sodium phosphate and dibasic sodium phosphate tablets. In the overwhelming majority of patients, electrolyte abnormalities were not associated with any adverse events.

In the monobasic sodium phosphate and dibasic sodium phosphate tablets phase 3 study, 96%, 96%, and 93% of patients who took 60 grams of Visicol, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, respectively, developed hyperphosphatemia (defined as phosphate level > 5.1 mg/dL) on the day of the colonoscopy. In this study, patients who took 60 grams of Visicol, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets had baseline mean phosphate levels of 3.5, 3.5, and 3.6 mg/dL and subsequently developed mean phosphate levels of 7.6, 7.9, and 7.1 mg/dL, respectively, on the day of the colonoscopy.

In the monobasic sodium phosphate and dibasic sodium phosphate tablets phase 3 study, 20%, 22%, and 18% of patients who took 60 grams of Visicol, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, respectively, developed hypokalemia (defined as a potassium level <3.4 mEq/L) on the day of the colonoscopy. In this study, patients who took 60 grams of Visicol, 60 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets, and 48 grams of monobasic sodium phosphate and dibasic sodium phosphate tablets all had baseline potassium levels of about 4.3 mEq/L and then developed a mean potassium level of 3.7 mEq/L on the day of the colonoscopy.

In the monobasic sodium phosphate and dibasic sodium phosphate tablets phase 3 trial, several patients on all three sodium phosphate regimens developed hypocalcemia and hypernatremia that did not require treatment.