Regulatory Decision Summary for Omnipaque

This Supplemental New Drug Submission (SNDS) Clinical and Chemistry & Manufacturing was filed to seek authorization for the addition of new routes of administration (oral for adults; oral and rectal for pediatrics), a new indication for radiographic imaging of the gastrointestinal tract (including esophagus, stomach, small bowel, and colon) in adults and pediatrics, and a new indication for computerized tomography (CT) of the abdomen and pelvis with or without intravenous administration of radiopaque contrast agent. Upon review, an adult and pediatric indication for radiographic imagining of the gastrointestinal tract (including esophagus, stomach, small bowel, and colon) and an adult and pediatric indication for CT of the abdomen and pelvis (limited for use) in conjunction with intravenous administration of Omnipaque are recommended.

This Supplemental New Drug Submission (SNDS) Clinical and Chemistry and Manufacturing was filed to seek authorization for the addition of new routes of administration (oral for adults; oral and rectal for pediatrics), a new indication for radiographic imaging of the gastrointestinal tract (including esophagus, stomach, small bowel, and colon) in adults and pediatrics, and a new indication for CT of the abdomen and pelvis with or without intravenous administration of radiopaque contrast agent. Upon review, an adult and pediatric indication for radiographic imagining of the gastrointestinal tract (including esophagus, stomach, small bowel, and colon) and an adult and pediatric indication for CT of the abdomen and pelvis (limited for use) in conjunction with intravenous administration of Omnipaque are recommended.

The proposed routes of administration and indications were supported by the results of six clinical trials (studies N-137, PS-632, PS-641, IOH-1058, N-121, and IOH-1030).

The adult indication of “OMNIPAQUE 300 and OMNIPAQUE 350 are indicated in adults for oral administration for radiographic imaging of the GI tract (including esophagus, stomach and small bowel and colon)” was supported by two pivotal phase 3 randomized, double-blind clinical trials (N-137 and PS-632) in which safety, tolerability, and efficacy were demonstrated. Study N-137 included 49 adult patients with possible gastrointestinal (GI) perforation and study PS-632 included 60 adult patients who required contrast examination of the GI tract. Compared to the active control gastrografin 370, orally administered OMNIPAQUE 350 had comparable or significantly better images of diagnostic quality (Study N-137: OMNIPAQUE 350 79% vs gastrografin 64%; Study PS-632: 72% vs 26%). In addition, the efficacy and safety of OMNIPAQUE 300 in adults for this indication were extrapolated from the results of a randomized, double-blind pediatric trial (Study IOH-1058), which enrolled four adolescent patients (11 - <18 years, mean body weight 45.13 kg) requiring contrast medium examination of the GI tract. These adolescent patients were dosed with a mean dose of OMNIPAQUE 300 similar to that of adults (i.e., 86.5 mL, 25.95 gI). The results showed a comparable efficacy and safety between the adolescent and adult populations, which supports an oral indication of OMNIPAQUE 300 for adult radiographic imagining of the GI tract.

The adult indication of “OMNIPAQUE 240, OMNIPAQUE 300, and OMNIPAQUE 350 diluted to 6 to 9 mg I/mL are indicated for oral administration in adults for CT of the abdomen and pelvis in conjunction with IV administration of OMNIPAQUE” was supported by Study PS-641. In this study, concomitant use of oral (diluted) and IV (undiluted) OMNIPAQUE was evaluated compared to with the active control gastrografin 282 for safety, taste/tolerability, and contrast-enhanced CT of the abdomen/pelvis in 170 adult patients requiring contrast-enhanced CT of the abdomen. The results demonstrated that OMNIPAQUE had significantly less adverse events compared to gastrografin 282 and was comparable to gastrografin 282 in terms of the of the diagnostic quality of the images (100% of images using both OMNIPAQUE and gastrografin produced images of diagnostic quality).

The pediatric indication of “OMNIPAQUE 240 and OMNIPAQUE 300 are indicated for oral, rectal, or by enteric tube administration for radiographic imaging of the GI tract (including esophagus, stomach, small bowel and colon)” was supported by one pivotal randomized, double-blind trial (study IOH-1058) and one supporting open label, non-comparative trial (study N-121). These studies evaluated the safety, taste/tolerability, and the clinical efficacy of OMNIPAQUE 140, 180, or 300 for radiographic imaging of the GI tract in pediatric patients. Study IOH-1058 included 89 pediatric patients < 18 years of age requiring contrast medium examination of the GI tract and Study N-121 included 30 pediatric patients 0 to 14 years of age requiring contrast-enhanced X-ray examination of the GI tract. The results from both trials showed favorable safety, tolerability, and tolerable taste for oral OMNIPAQUE. Study IOH-1058 also demonstrated a comparable rate of images of sufficient quality for diagnostic assessment for OMNIPAQUE and the active control barium sulfate (OMNIPAQUE 88.9% vs barium sulfate 96.1%). Although OMNIPAQUE 240 was not included in Study IOH-1058 or Study N-121, the safety and efficacy of OMNIPAQUE 180 and 300 were adequately demonstrated and therefore the proposed use of OMNIPAQUE 240 is considered to be acceptable.

The pediatric indication of “OMNIPAQUE 240, OMNIPAQUE 300, and OMNIPAQUE 350 diluted to 9 to 29 mg I/mL are indicated for oral administration in children for CT of the abdomen and pelvis in conjunction with IV administration of OMNIPAQUE” was supported by an open label, non-comparative study (IOH-1030). This study included 70 pediatric patients < 18 years of age who required a contrast-enhanced CT of the abdomen. The trial results demonstrated that an age-appropriate diluted oral dosing of OMNIPAQUE (9 to 29 mg I/ml) and a body-weight based IV dosing of OMNIPAQUE 240 or 300 was safe for use. Used in conjunction with IV OMNIPAQUE 240 or 300 for contrast-enhanced CT examination of abdomen and pelvis, the study showed that 100% of radiographic visualizations were of diagnostic quality.

Orally/enterically and/or rectally administered Omnipaque was generally well tolerated in the clinical trials. The most frequent adverse reaction reported in adults following oral administration was diarrhea/stools loose with an incidence of 32.4%, followed by nausea (5.4%), abdominal cramps/colic/stomach ache (4.6%), vomiting (4.2%), pain (2.7%), and headache (1.5%). The most frequent adverse reaction reported in pediatrics was diarrhea/loose stools with an incidence of 21.9%, followed by vomiting (3.7%), nausea (1.7%), and fever (1.3%). Adverse reactions were all considered to be mild and resolved without sequelae and within hours.

Based on the safety and efficacy data reviewed, the benefit-harm-uncertainty profile for Omnipaque continues to be favourable when used via the oral or rectal routes of administration under the conditions of use recommended in the Omnipaque Product Monograph at this time. An adult and pediatric indication for radiographic imagining of the gastrointestinal tract (including esophagus, stomach, small bowel, and colon) and an adult and pediatric indication for CT of the abdomen and pelvis (limited for use) in conjunction with intravenous administration of Omnipaque are recommended. A Notice of Compliance (NOC) pursuant to section C.08.004 of the Food and Drug Regulations is recommended.

For further details about Omnipaque, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.