MON-388 - Effect of North Star Desiccated Thyroid Extract vs Levothyroxine on Vital Signs and Lipids in Adults With Hypothyroidism: A Phase 2 Randomized Trial

Hypothyroidism is associated with dyslipidemia and increased cardiovascular (CV) risk. Desiccated thyroid extracts (DTEs), porcine-derived pharmaceutical preparations containing thyroxine and triiodothyronine, have been used for over a century, but not yet reviewed by the U.S. Food & Drug Administration for safety or efficacy. Herein, we examined vital signs and lipid markers in adults with hypothyroidism treated with North Star DTE or levothyroxine (LT4) in the phase 2, randomized, NorthStar-02-001 trial (NCT05712421).

This phase 2, double-blind, randomized, parallel-group study included 18-75 year old adults with primary hypothyroidism on stable LT4 dose for ≥12 weeks and in-range thyrotropin (TSH) levels (0.35–5.50 mIU/L) at screening. 302 subjects were randomized 2:1 to DTE or LT4 arms. DTE starting dose was based on LT4 dose using a published dose conversion ratio (100 µg LT4: 68 mg DTE). Treatment was once daily for 30 weeks: an 18-week titration period (dose adjusted every 6 weeks to maintain target TSH) followed by a 12-week stable-dose period. Patients were excluded if weight < 60 or > 120 kg; resting heart rate (HR) < 48 bpm; abnormal/clinically significant electrocardiogram (ECG) at screening or baseline; sitting systolic blood pressure (SBP) > 165 or < 80 mmHg; or diastolic blood pressure (DBP) > 95 or < 40 mmHg. Vital signs were assessed as part of safety evaluation and change from baseline in lipid profile was an exploratory endpoint.
Safety analysis included all subjects receiving ≥ 1 dose (DTE, n=198; LT4, n=100). No trends or major intergroup differences in body weight or vital signs were observed over 30 weeks. At Week 30, mean changes in weight (DTE, 0.83 kg; LT4, 0.96 kg), SBP (DTE, -2.1 mmHg; LT4, -0.6 mmHg), and DBP (DTE, -1.2 mmHg; LT4, -0.9 mmHg) from baseline were minimal. ECG profiles were also similar, with no safety signals observed. In a prespecified analysis, there were 4 and 11 occurrences of HR < 50 bpm in the LT4 and DTE groups, respectively, and 3 HR > 100 bpm events in the DTE group over 30 weeks. 9 and 12 LT4- and DTE-treated subjects, respectively, reported CV-related treatment-emergent adverse events, with only bradycardia reported by ≥ 3 subjects in both groups. A CV-related treatment-emergent serious adverse event (myocardial infarction) deemed possibly related to study drug occurred in 1 DTE-treated subject. There were no clinically meaningful changes in lipid profile. At Week 30, both groups had minimal or no changes from baseline in mean cholesterol (DTE, -0.14 mmol/L; LT4, 0.11 mmol/L), HDL (DTE, -0.02 mmol/L; LT4, 0.01 mmol/L), LDL (DTE, -0.10 mmol/L; LT4, 0.00 mmol/L), and triglycerides (both, 0.01 mmol/L).

North Star DTE was generally well-tolerated in the phase 2 NorthStar-02-001 trial. Though a small subset of subjects exhibited HR values outside predefined thresholds, the SBP, DBP, HR, and lipid profiles remained clinically comparable between DTE and LT4 groups.

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