p; Abdominal discomfort 6 (21)
Abdominal distension 6 (21)
Constipation 6 (21)
Flatulence 6 (21)
Gastroesophageal reflux disease 3 (10)
Defecation urgency 3 (10)
Rectal tenesmus 3 (10)
Infections
Influenza 6 (21)
Nasopharyngitis 5 (17)
Gastroenteritis 4 (14)
Investigations
Decreased weight 7 (24)
Increased ALT 5 (17)
General Disorders
Chest pain 7 (24)
Fatigue 5 (17)
Fever 3 (10)
Musculoskeletal Disorders
Back pain 4 (14)
Nervous System Disorders
Headache 3 (10)
Dizziness 3 (10)
Respiratory Disorders
Pharyngolaryngeal pain 4 (14)
Nasal congestion 3 (10)
Cardiac Disorders
Angina pectoris 3 (10)
Palpitations 3 (10)
Adverse reactions of severe intensity were reported by 8 (28%) of 29 patients, with the most common being diarrhea (4 patients, 14%), vomiting (3 patients, 10%), increased ALT or hepatotoxicity (3 patients, 10%), and abdominal pain, distension, and/or discomfort (2 patients, 7%).
Transaminase Elevations
During the HoFH clinical trial, 10 (34%) of 29 patients had at least one elevation in ALT and/or AST ≥3x ULN (see Table 4). No clinically meaningful elevations in total bilirubin or alkaline phosphatase were observed. Transaminases typically fell within one to four weeks of reducing the dose or withholding JUXTAPID.
Table 4: Patient Incidence of Transaminase Elevations During the HoFH Clinical Trial Upper limits of normal (ULN) ranged from 33-41 international units/L for ALT and 36-43 international units/L for AST.
N (%)
Total Patients 29
Maximum ALT
≥3 to <5 x ULN 6 (21%)
≥5 to <10 x ULN 3 (10%)
≥10 to <20 x ULN 1 (3%)
≥20 x ULN 0
Maximum AST
≥3 to <5 x ULN 5 (17%)
≥5 to <10 x ULN 1 (3%)
≥10 to <20 x ULN 0
≥20 x ULN 0
Among the 19 patients who enrolled in an extension study following the HoFH clinical trial, one discontinued because of increased transaminases that persisted despite several dose reductions, and one temporarily discontinued because of markedly elevated transaminases (ALT 24x ULN, AST 13x ULN) that had several possible causes, including a drug-drug interaction between JUXTAPID and the strong CYP3A4 inhibitor clarithromycin [see Drug Interactions (7.1)].
Hepatic Steatosis
Hepatic fat was prospectively measured using magnetic resonance spectroscopy (MRS) in all eligible patients during the HoFH clinical trial. After 26 weeks, the median absolute increase in hepatic fat from baseline was 6%, and the mean absolute increase was 8% (range, 0% to 30%). After 78 weeks, the median absolute increase in hepatic fat from baseline was 6%, and the mean absolute increase was 7% (range, 0% to 18%). Among the 23 patients with eva luable data, on at least one occasion during the trial, 18 (78%) exhibited an increase in hepatic fat >5% and 3 (13%
