Axona

Axona Professional Information

SIDE EFFECTS

Clinical Study Experience

Thus far, a total of 197 subjects have received Axona in one of 3 clinical trials. Because clinical studies are conducted under varying conditions, AE rates cannot be directly compared to rates in clinical studies of other compounds, and may not reflect the rates observed in practice.

Single-Administration Study

The first clinical trial was a randomized, placebo-controlled, crossover-design study to measure the potential therapeutic effects on memory of a single administration of Axona (40-80 grams of MCTs) in 20 patients between the ages of 55-85 years old and diagnosed with probable AD (n = 15) or mild cognitive impairment (MCI) (n = 5).12 Two subjects experienced AEs primarily associated with the GI system, including nausea, abdominal discomfort, and diarrhea.

Alzheimer's Disease Study

The second clinical study was a double-blind (DB), randomized, 90-day, placebo-controlled study performed at multiple US clinical centers in a population of 152 patients with mild to moderate AD.¹³ In addition, subjects completing the 90-day trial were permitted to enroll in an optional 6-month, open-label (OL) extension study. Patients received 10 grams of caprylic triglyceride per day on days 1-7 and 20 grams of caprylic triglyceride per day on days 8-90. Seventy-six percent of Axona subjects (compared with 62% of placebo subjects) experienced at least one AE during the course of the study, the majority of which were mild to moderate in severity. The most frequently reported AEs involved the GI system, in which 48.8% of Axona and 27.3% of placebo subjects experienced one or more AEs. The primary GI AEs occurring more frequently in the Axona than in the placebo group consisted of: diarrhea (24.4% vs 13.6%), flatulence (17.4% vs 7.6%), and dyspepsia (9.3% vs 4.5%). AEs reported among the 49 subjects in the OL phase of the study were consistent with those observed in the DB phase.

The following table presents the number and percentage of AD patients in the DB AD study who developed the most commonly reported AEs (occurring more frequently in Axona than in placebo subjects and in at least 3% of patients receiving Axona).

Adverse Events Reported in ≥ 3% of Axona Patients*

Bridging Study

The third clinical study was a 14-day, open-label, randomized trial performed at 4 US clinical centers in 66 normal elderly volunteers. Three formulations of Axona were administered for 14 days either with a 7-day titration (7 days at 10 grams caprylic triglyceride followed by 7 days at 20 grams caprylic triglyceride) or without titration (14 days at 20 grams caprylic triglyceride). The original formulation utilized in the DB AD study was compared with 2 formulations that contained different ratios of proteins to carbohydrates. Subjects within each cohort experienced comparable frequencies of AEs, including those within the GI system. The most common AEs, consisting of nausea (19.7%), abdominal distension (16.7%), flatulence (15.2%), and diarrhea (13.6%), were generally transient in nature and resolved without treatment. In addition, 7 subjects developed clinically significant increases in triglyceride values after Axona administration. Six of these 7 subjects were identified as having probable metabolic syndrome. Of note, dietary restrictions were not imposed during this study, and neither the quantity nor the quality of food consumption was monitored. Therefore, although a causal relationship to Axona was not determined, triglyceride levels should be periodically monitored in patients receiving Axona who meet criteria indicative of metabolic syndrome.

Gastrointestinal

In each of the 3 clinical studies, AEs occurring within the GI system were the most commonly experienced events, and in general, the most frequently reported AEs consisted of diarrhea, flatulence, and dyspepsia. Mild “queasiness” or nausea that was transient in nature was also occasionally reported, as were “bloating” and abdominal discomfort. In the DB AD study, the overall rate of severe GI events in Axona patients included diarrhea (5.8%), dyspepsia (2.3%), and flatulence (1.2%). In all but 2 cases, the diarrhea spontaneously resolved without treatment. The majority of GI events were mild to moderate in severity, and it was found that the severity of AEs could be reduced if Axona was taken with food. In the DB AD study, the incidence of severe diarrhea declined from 9.7% to 3.1% following a change in mixing instructions (blending the original formulation of Axona with a meal replacement drink such as Ensure® instead of water). The marketed formulation of Axona does not require mixing with Ensure (see “Clinical Studies” and “HOW SUPPLIED/Storage and Handling” below).

Renal Function

In the DB AD clinical study, mean values in BUN, uric acid, and creatinine increased from screening values in the Axona group; however, in 5 of 7 cases these laboratory increases did not exceed 1.5 x ULN. One subject with a recent history of renal failure requiring dialysis had an elevated BUN value that was 2.4 x ULN. Another patient who had been receiving long-term therapy with medications associated with elevated renal function test results (ie, an angiotension II receptor antagonist and furosemide) developed increased BUN and creatinine values up to 2.5 x ULN. The majority of subjects with significant renal function test abnormalities were also noted to have abnormal values at screening, were taking concomitant medications associated with elevated renal function test results, and had BUN/creatinine ratios > 15, indicative of dehydration. While the increases in these renal function tests appear to be related to either pre-existing conditions or to dehydration, a relation to Axona cannot be entirely ruled out.

Other Notable Adverse Reactions

In the DB AD study, a 93-year-old AD patient with a history of IBS and intermittent diarrhea, along with multiple cardiac abnormalities including left ventricular hypertrophy, expired due to a GI bleed following 28 days of Axona administration. Also in the DB AD study, an 87-year-old patient with a history of diverticulitis and stomach ulcer was found to have a guaiac-positive stool when hospitalized for pneumonia. This patient was discharged from hospital without sequelae. All of these events were likely to be related to the subjects' underlying comorbidities; however, the possibility that Axona may exacerbate pre-existing GI inflammatory processes should be considered.

Voluntarily Reported Post-Market AEs

Consistent with AEs reported during clinical trials, spontaneously reported AEs consisted primarily of abdominal discomfort, diarrhea, nausea, and dyspepsia. Fainting and dizziness were also reported in < 1 in 500 patients taking Axona (see “WARNINGS AND PRECAUTIONS”). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to exposure to the product.

Read the entire FDA prescribing information for Axona (Caprylidene Prescription Medical Food)