Mycapssa (Page 5 of 6)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in laboratory animals have demonstrated no mutagenic potential of octreotide acetate.

No carcinogenicity studies have been conducted with MYCAPSSA. No carcinogenic potential was demonstrated in mice treated subcutaneously with octreotide acetate for 85–99 weeks at doses up to 2000 mcg/kg/day (8 times the clinical dose based on octreotide injection body surface area). In a 116-week subcutaneous study in rats administered octreotide acetate, a 27% and 12% incidence of injection-site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1250 mcg/kg/day (10 times the clinical dose based on octreotide injection body surface area) compared to an incidence of 8% to 10% in the vehicle-control groups. The increased incidence of injection-site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. There was also a 15% incidence of uterine adenocarcinomas in the 1250 mcg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats, which does not occur in humans.

No fertility studies in animals have been conducted with MYCAPSSA. Injectable octreotide acetate did not impair fertility in rats at doses up to 1000 mcg/kg/day, which represents 7 times the clinical dose based on octreotide injection body surface area.

14 CLINICAL STUDIES

The efficacy of MYCAPSSA was established in a 9 month, randomized, double-blind, placebo-controlled study (NCT03252353) that enrolled 56 patients with acromegaly.

In the overall study population, 54% were female and the average age of patients was 55 years. 91% of patients were Caucasian, 5% Asian, 2% Black, and 2% Other. The percentage of patients with previous pituitary surgery was 88%. The baseline IGF-1 levels (the average of 2 assessments measured within 2 weeks of randomization) was 0.80 times ULN (range: 0.5–1.1 times ULN) in the patients treated with MYCAPSSA and 0.84 times ULN (range: 0.3–1.1 times ULN) in patients treated with the placebo.

In this study, patients initiated MYCAPSSA treatment twice daily 1 month after their last injection of somatostatin analogs. The starting dose was 40 mg (20 mg in the morning and 20 mg in the evening). Dose increase was allowed during dose titration to 60 mg (40 mg in the morning and 20 mg in the evening) and to a maximal dose of 80 mg daily (40 mg in the morning and 40 mg in the evening) until patients were deemed adequately controlled based on biochemical results and/or clinical judgement. Patients then maintained their target dose until end of treatment.

The primary efficacy endpoint was somatostatin dose-adjusted proportion of patients who maintain their biochemical response, defined as an IGF-1 levels less than or equal to the ULN at the end of 9 months of treatment. 58% of patients treated with MYCAPSSA vs. 19% of patients treated with placebo maintained their biochemical response.

25% of patients treated with MYCAPSSA required discontinuation of MYCAPSSA and treatment with other somatostatin analogs at some point during the 9-month study. Criteria for somatostatin analog rescue were IGF-1 levels ≥ 1.3 times ULN and exacerbation of acromegaly signs and symptoms on two consecutive assessments while treated for at least 2 weeks with 80 mg/day or other reasons such as adverse reactions or patient’s decision.

16 HOW SUPPLIED/STORAGE AND HANDLING

MYCAPSSA delayed-release 20 mg capsules are white hard gelatin capsules imprinted with “OT” on one half of the capsule and “20” on the other half.

The capsules are supplied as:

NDC Number	Package Size
69880-120-28	Wallet of 28 capsules

Storage

Until first use, store unopened wallets of MYCAPSSA refrigerated at 2° to 8°C (36° to 46°F). Do not freeze.

After first use, opened wallets may be stored at 20° to 25°C (68° to 77°F) for up to 1 month.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Cholelithiasis and Complications of Cholelithiasis

Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis and pancreatitis) [see Warnings and Precautions (‎5.1)].

Hypoglycemia and Hyperglycemia

Advise patients to contact their healthcare provider if they have problems with blood sugar levels, either hyperglycemia or hypoglycemia [see Warnings and Precautions (‎5.2)].

Thyroid Function Abnormalities

Inform patients that their thyroid function will be assessed periodically during treatment [see Warnings and Precautions (‎5.3)].

Cardiac Function Abnormalities

Inform patients to contact the health care provider in case they notice irregular heartbeat [see Warnings and Precautions (‎5.4)].

Decreased Vitamin B₁₂ Levels and Abnormal Schilling’s Tests

Inform patients that Vitamin B₁₂ levels may be monitored during the treatment [see Warnings and Precautions (‎5.5)].

Females and Males of Reproductive Potential

Inform female patients that treatment with MYCAPSSA may result in unintended pregnancy [see Use in Specific Populations (‎8.3)].

Rx ONLY

Manufactured by MW Encap Ltd., Scotland, UK.

©2022 Amryt Pharmaceuticals, Inc. Mycapssa is a registered trademark of the Amryt Pharma Group. All rights reserved

Revised: 03/2022

Patient Information MYCAPSSA® [my (as in sky)-cap-sah] (octreotide) delayed-release capsules, for oral use
This Patient Information has been approved by the U.S. Food and Drug Administration.				Approved: 06/2020
What is MYCAPSSA?
MYCAPSSA is an oral prescription medicine used in the long-term maintenance treatment of acromegaly in people for whom initial treatment with octreotide or lanreotide has been effective and tolerated. It is not known if MYCAPSSA is safe and effective in children.
Do not take MYCAPSSA if you:
are allergic to octreotide acetate or any of the ingredients in MYCAPSSA. MYCAPSSA can cause a serious allergic reaction including anaphylactic shock. Stop taking MYCAPSSA right away and get emergency help if you have any of these symptoms:
		swelling of your tongue, throat, lips, eyes or face severe itching of the skin with rash or raised bumps chest pain		trouble swallowing or breathing feeling faint rapid heart beat
See the end of this leaflet for a complete list of ingredients in MYCAPSSA.
Before you take MYCAPSSA, tell your healthcare provider about all of your medical conditions, including if you:
have liver cirrhosis or liver problems have kidney problems are pregnant or plan to become pregnant. It is not known if MYCAPSSA will harm your unborn baby. MYCAPSSA may increase your chance of becoming pregnant. are breastfeeding or plan to breastfeed. It is not known if MYCAPSSA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take MYCAPSSA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
MYCAPSSA may affect the way other medicines work, and other medicines may affect how MYCAPSSA works.
Especially tell your healthcare provider if you take oral contraceptives. Use an alternative non-hormonal method of contraception or a back-up method while taking MYCAPSSA.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take MYCAPSSA?
Read the detailed “Instructions for Use” at the end of this Patient Information about the right way to take MYCAPSSA. Take MYCAPSSA exactly as your healthcare provider tells you to take it. Take MYCAPSSA with a glass of water on an empty stomach. Take MYCAPSSA at least 1 hour before a meal or at least 2 hours after a meal (for example, you could take your morning dose 1 hour before breakfast and your evening dose at bedtime).
Swallow the capsules whole. Do not crush or chew the capsules before swallowing.
What are the possible side effects of MYCAPSSA?
	gallbladder problems. MYCAPSSA may cause problems with the gallbladder. Tell your healthcare provider if you have sudden pain in your upper right stomach (abdomen), sudden pain in your right shoulder or between your shoulder blades, yellowing of your skin or the whites of your eyes, fever with chills, nausea blood sugar problems. MYCAPSSA may cause you to have high blood sugar (hyperglycemia), low blood sugar (hypoglycemia), or diabetes. Tell your healthcare provider if you have problems with high or low blood sugar. Your healthcare provider will check your blood sugar when you start taking MYCAPSSA or when your dose is changed. thyroid problems. MYCAPSSA may keep your thyroid from releasing thyroid hormones leading to hypothyroidism. Your thyroid function will be checked regularly during your treatment with MYCAPSSA. heart rhythm problems. Tell your healthcare provider if you have an irregular heartbeat (your heart is not beating normally). low vitamin B12 levels in your blood. Your healthcare provider may check your vitamin B12 levels during treatment with MYCAPSSA.
The most common side effects of MYCAPSSA include:
	headache nausea diarrhea		joint pain weakness sweating a lot
These are not all the possible side effects of MYCAPSSA. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store MYCAPSSA?
Before first use, store unopened wallets of MYCAPSSA in a refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. After first use, store opened wallets at room temperature between 68°F to 77°F (20°C to 25°C) for up to 1 month.
Keep MYCAPSSA and all medicines out of the reach of children.
General information about the safe and effective use of MYCAPSSA.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information. Do not use MYCAPSSA for a condition for which it was not prescribed. Do not give MYCAPSSA to other people, even if they have the same symptoms you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about MYCAPSSA that is written for health professionals.
What are the ingredients in MYCAPSSA?
Active ingredient: octreotide acetate
Inactive ingredients: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE® (methacrylate).
Amryt Pharmaceuticals DAC.Dublin, Ireland
For more information about MYCAPSSA call the medical information department at 1-855-303-2347 or medinfo@amrytpharma.com or go to www.MYCAPSSA.com and select patient information.