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Akrimax Announces Publication of the CONTROL Switch Study

Additional Results from the CONTROL Study Program

 

Cranford, NJ – December, 2016 – Akrimax Pharmaceuticals announced that results from the CONTROL Switch Study have been published in the journal Drugs in R&D. CONTROL Switch is the first study to document the clinical effects of switching patients from tablet formulations of levothyroxine to a gel cap formulation. Specifically, the study examined changes in laboratory test values, the number of dose titrations experienced and improvements in hypothyroid symptom status after the medication change. Thyroid hormone therapy with oral levothyroxine is one of the most frequently used medications in the US with over 115 million prescriptions dispensed in 2013.¹

The CONTROL Switch study was conducted using the medical records of 99 randomly selected hypothyroid patients undergoing levothyroxine treatment for a minimum of one year. Patient records were selected by using electronic medical record systems from participating study sites. Records that met the study criteria were chosen for manual review by a trained nurse abstractor using an IRB-approved data collection form. The data collected (six months pre switch; six months post switch) was then reviewed, verified and committed to a database for prespecified statistical analysis.

The CONTROL Switch Study analyzed the reasons for levothyroxine dose or formulation changes as well as improvements in key parameters of hypothyroidism treatment that may have occurred as a result of switching from traditional levothyroxine tablet therapy to a gel cap formulation. These parameters included the percentage of patients achieving their target TSH values as recommended by current treatment guidelines, the percentage of patients experiencing levothyroxine dose changes and the percentage of patients who experienced improvement in hypothyroid symptom status post switch. Other data collected included relevant patient characteristics such as the presence of GI disorders known to affect the tolerability or absorption of levothyroxine tablet formulations.

The results of CONTROL Switch demonstrate no significant difference in TSH status after switching from a tablet formulation of levothyroxine to a gel cap formulation. However, significant reductions were observed in the number dose changes experienced as well as significant improvements in hypothyroid symptoms after the medication switch. Among the full cohort of 99 patients, 85.8% experienced one or fewer dose changes post switch. The post-switch mean of 0.73 ± 0.96 dose adjustments per patient is a 54.7% decrease in the pre-switch number of dose adjustments. Among the full cohort of 99 patients, 61.6% had physician-reported improvements of hypothyroid symptoms following the switch to the gel cap formulation. These results were consistent regardless of reason for medication switch (efficacy or adverse effects) or prior therapy (branded or generic levothyroxine tablets).

“Levothyroxine dose and medication changes are common in clinical practice that may also contribute to unnecessary utilization of healthcare resources and patient dissatisfaction with care”, stated Walter Sandulli, VP of Marketing at Akrimax and study co-author. “Our study suggests that for some patients, a strategy of switching from traditional levothyroxine tablets to levothyroxine gel caps may eliminate or lower the need for such changes while improving hypothyroid symptom control.”

The CONTROL Surveillance Project is part of a five-part program that also includes the CONTROL Surveillance Project, the CONTROL HE (health economics) Study, the CONTROL TS (treatment satisfaction) Study, and the CONTROL Registry. The objective of this scientific program is to document the issues and costs related to levothyroxine use in real-world clinical settings.

“The CONTROL Study Program will help better describe the impact of malabsorption, tolerability and other clinical complications that are commonly observed with tablet formulations of levothyroxine”, Sandulli stated. “These studies reaffirm Akrimax’s commitment to improving the care of patients with hypothyroidism.”

The protocols for all CONTROL studies were reviewed and approved by licensed Institutional Review Boards (IRBs) in accordance with US federal guidelines. Results of the CONTROL Surveillance Project were reported in the January, 2016 edition of Drugs in R&D. The results of the CONTROL HE Study were reported in the November, 2016 online edition of Clinical Drug Investigations. The results of the CONTROL TS Study was presented at the 2016 American Thyroid Association annual conference in Denver, CO. A summary abstract is available in a special online edition of Thyroid, the journal of the American Thyroid Association, and can be found at http://online.liebertpub.com/thy.

About Akrimax Pharmaceuticals

Since 2011 Akrimax and IBSA have worked in collaboration to market Tirosint® (levothyroxine sodium capsules) a unique treatment for hypothyroidism. Tirosint is formulated with just four ingredients: levothyroxine, gelatin, glycerin and water. Clinical studies suggest that Tirosint may be an effective alternative for patients who suffer from tolerability or absorption problems that may be experienced with traditional levothyroxine tablet formulations.

For Full Prescribing Information including Black Box Warning go to www.Tirosint.com.

About Hypothyroidism

Hypothyroidism is an endocrine disorder with numerous causes resulting in a deficiency in thyroid hormone. More than 27 million adults have been diagnosed with hypothyroidism.² Up to 13 million Americans have undiagnosed hypothyroidism.³ About 2% of the U.S. population has pronounced hypothyroidism, and as much as 10% has subclinical (mild) hypothyroidism. The condition is most common in women over 40 years of age and in the elderly of both sexes.⁴ The signs and symptoms of hypothyroidism are nonspecific and may include fatigue, forgetfulness, depression, constipation, muscle cramps, weight gain, dry skin and hair loss.⁵ Laboratory tests (TSH, FT3 and FT4) are the most common way hypothyroidism is detected. Treatment with levothyroxine sodium oral tablets is the standard of care in hypothyroidism.

About Tirosint® (levothyroxine sodium) capsules

Tirosint (levothyroxine sodium) is the first and only levothyroxine therapy in a liquid gel cap. Tirosint gel caps are pure. Tirosint gel caps contain only T4, water, glycerin, and gelatin.

Tirosint is available in 10 dosage strengths, including an exclusive 13 microgram dose. Tirosint is administered as a single daily dose, preferably one-half to one-hour before breakfast. Tirosint should be taken at least 4 hours apart from drugs that are known to interfere with its absorption. Tirosint capsules cannot be cut or crushed. Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4-6 weeks.

Tirosint capsules are housed in blister packs to protect it from light and moisture. Blister packs are clearly marked for daily dosing. Tirosint should be protected from light and moisture and stored at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F).

IMPORTANT SAFETY INFORMATION


WARNINGS

Thyroid hormones, including TIROSINT, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

In patients with nontoxic diffuse goiter or nodular thyroid disease, particularly the elderly or those with underlying cardiovascular disease, levothyroxine sodium therapy is contraindicated if the serum TSH level is already suppressed due to the risk of precipitating overt thyrotoxicosis. If the serum TSH level is not suppressed, TIROSINT should be used with caution in conjunction with careful monitoring of thyroid function for evidence of hyperthyroidism and clinical monitoring for potential associated adverse cardiovascular signs and symptoms of hyperthyroidism.

CONTRAINDICATIONS

Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T3 and T4 levels) or overt thyrotoxicosis of any etiology and in patients with acute myocardial infarction. Levothyroxine is contraindicated in patients with uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance of glucocorticoids. TIROSINT is contraindicated in patients with hypersensitivity to any of the inactive ingredients in TIROSINT capsules. TIROSINT is also contraindicated for anyone who may be unable to swallow a capsule (e.g., infants, small children).

PRECAUTIONS

Effects on bone mineral density – In women, long-term levothyroxine sodium therapy has been associated with increased bone resorption, thereby decreasing bone mineral density, especially in postmenopausal women on greater than replacement doses or in women who are receiving suppressive doses of levothyroxine sodium. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed serum parathyroid hormone levels. Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum dose necessary to achieve the desired clinical and biochemical response.

Patients with underlying cardiovascular disease – Exercise caution when administering levothyroxine to patients with cardiovascular disorders and to the elderly in whom there is an increased risk of occult cardiac disease. In these patients, levothyroxine therapy should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease and it should be noted that unlike levothyroxine sodium tablets, TIROSINT capsules cannot be cut in half. If cardiac symptoms develop or worsen, the levothyroxine dose should be reduced or withheld for one week and then cautiously restarted at a lower dose. Overtreatment with levothyroxine sodium may have adverse cardiovascular effects such as an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias. Patients with coronary artery disease who are receiving levothyroxine therapy should be monitored closely during surgical procedures, since the possibility of precipitating cardiac arrhythmias may be greater in those treated with levothyroxine. Concomitant administration of levothyroxine and sympathomimetic agents to patients with coronary artery disease may precipitate coronary insufficiency.

ADVERSE REACTIONS

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage such as fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, and other adverse reactions. This is not an exhaustive list. Please refer to TIROSINT’s full Prescribing Information for a more comprehensive list of adverse reactions associated with hyperthyroidism.

About Akrimax Pharmaceuticals

Akrimax Pharmaceuticals, LLC is a privately held, innovative specialty pharmaceutical company that acquires, develops and markets advanced ethical prescription medications. For more information, visit www.akrimax.com.

References

1. IMS Institute for Healthcare Informatics Report, “Medicine Use and the Shifting Costs of Healthcare”; 2014; pg. 46

2. Booth, M, 2019. Published online at: http://www.reviewjournal.com/life/health/thyroid-disease-common-us

3. Canaris GJ, Manowitz NR, Mayor G, Ridgeway EC, "The Colorado Thyroid Disease Prevalence Study", Arch of Internal Medicine; 2000;160: 526-534

4. McDermott MT. "In the clinic: hypothyroidism". Annals of Internal Medicine; 2009;151 (11): ITC-6-1

5. Mathur, R, "Hypothyroidism", 2015. Published online at http://www.medicinenet.com/hypothyroidism/page5.htm


Contacts

J. Gregory Ford, Akrimax (Business Development), 908-372-1232, gford@akrimax.com