MedCheck: High-Dose Naloxone, Tavapadon, Tirzepatide, and Lumateperone

FDA Approves High-Dose Naloxone Nasal Spray for Opioid Overdose

In April the Food and Drug Administration (FDA) approved Rezenopy (naloxone hydrochloride) nasal spray for the treatment of known or suspected opioid overdose in adults and children, the agency announced. Rezenopy delivers 10 mg of naloxone hydrochloride in a single spray into one nostril.

If a person does not respond within two to three minutes or responds and then relapses into respiratory depression, an additional dose of Rezenopy may be given into the other nostril with a new device.

In a pharmacokinetic study of 30 healthy adult volunteers who received one dose of Rezenopy, the most common adverse reactions were abdominal pain, upper inflammation of the nasal passages and pharynx, and a foul taste in the mouth.

Rezenopy manufacturer Summit Biosciences Inc., which was acquired by Kindeva Drug Delivery in January, has not released a launch date.

Tavapadon Promising for Motor Control Problems in Parkinson’s

Patients with Parkinson’s disease who took the D1/D5 receptor partial agonist tavapadon in the Phase 3 TEMPO-3 trial experienced more time without troublesome dyskinesia than those who took placebo, Cerevel Therapeutics announced in April. The TEMPO-3 trial evaluated the efficacy, safety, and tolerability of tavapadon as an adjunctive therapy to levodopa in adults.

A total of 507 adults aged 40 to 80 years were enrolled in the trial. All had a confirmed diagnosis of Parkinson’s disease, were experiencing motor fluctuations, and were on a stable dose of levodopa for at least four weeks prior to screening. Patients kept taking their levopdopa and were randomized to receive either tavapadon, titrated to 5 mg to 15 mg, or placebo orally and once per day, for 27 weeks.

Patients were given a home diary known as a Hauser diary to record their motor function status in half-hour increments throughout the day. The primary endpoint was change from baseline in the average time without troublesome dyskinesia across two days, based on Hauser diary self-reports. Patients who took tavapadon and levodopa had an average increase of 1.7 hours in total time without troublesome dyskinesia per day compared with 0.6 hours per day among those treated with levodopa and placebo.

Tirzepatide Effective For Obese Patients With Obstructive Sleep Apnea

Obese patients with obstructive sleep apnea (OSA) who took tirzepatide in the SURMOUNT-OSA trial experienced an improvement in their sleep apnea symptoms compared with patients who did not take tirzepatide, Eli Lilly and Co. announced in April. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist and is found in Mounjaro for type 2 diabetes and Zepbound for chronic weight management.

The SURMOUNT-OSA Study 1 evaluated tirzepatide for 52 weeks in adults who had moderate-to-severe OSA, were obese, and who were not on positive airway pressure (PAP) therapy. Symptoms were measured using the apnea-hypopnea index (AHI), which records the number of times a person’s breathing shows a restricted or complete block of airflow per hour of sleep. At 52 weeks, adults taking tirzepatide had a mean AHI reduction from baseline of 27.4 events per hour, compared with a reduction of 4.8 events per hour among adults taking placebo.

The SURMOUNT-OSA Study 2 was similar but evaluated adults who were on and planned to continue to use PAP therapy. At 52 weeks, adults taking tirzepatide had a mean AHI reduction from baseline of 30.4 events per hour compared with a reduction of 6.0 events per hour among adults taking placebo.

In both SURMOUNT-OSA studies, adults taking tirzepatide had significantly more weight loss than those taking placebo.

Lumateperone Helpful as Adjunctive Therapy for Major Depressive Disorder

Patients with major depressive disorder who took lumateperone as an adjunctive therapy to their antidepressants showed significantly greater improvements in depressive symptoms than those who took placebo, Intra-Cellular Therapies announced in April. Lumateperone is an atypical antipsychotic currently marketed under the brand name Caplyta for the treatment of schizophrenia and for depressive episodes that are associated with bipolar I or II disorder.

In Study 501, 485 patients with major depressive disorder were randomized to receive 42 mg of lumateperone or placebo once per day along with their usual antidepressants. At baseline, Montgomery-Åsberg Depression Rating Scale (MADRS) total scores were 30.4 for the lumateperone group and 30.0 for the placebo group. At week 6, patients in the lumateperone group experienced a mean reduction in MADRS score of 14.7 points, compared with 9.8 points in the placebo group.

Lumateperone was generally well tolerated. The most common treatment-related adverse events observed were dry mouth, fatigue, and tremor. ■