Serostim

Somatropin is a form of human growth hormone. Human growth hormone is important in the body for the growth of bones and muscles.

Somatropin is used to treat growth failure in children and adults who lack natural growth hormone, and in those with chronic kidney failure, Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth, and other causes. Somatropin is also used to prevent severe weight loss in people with AIDS, or to treat short bowel syndrome.

Somatropin may also be used for purposes not listed in this medication guide.

If you use Zorbtive to treat short bowel syndrome, avoid drinking fruit juices or soda beverages. Follow the instructions of your doctor or nutrition counselor about what types of liquids you should drink while using Zorbtive.

Avoid drinking alcohol if you have short bowel syndrome. Alcohol can irritate your stomach and could make your condition worse.

This section provides information on the proper use of a number of products that contain somatropin, mammalian derived. It may not be specific to Serostim. Please read with care.

This medicine is given as a shot under your skin or into a muscle. Somatropin may sometimes be given at home to patients who do not need to be in the hospital. If you are using this medicine at home, your doctor will teach you how to prepare and inject the medicine. Be sure that you understand exactly how the medicine is prepared and injected.

If you are using this medicine to treat short bowel syndrome, carefully follow your doctor's instructions about any special diet. Take all other medicines or supplements your doctor has prescribed as part of your combination treatment.

This medicine comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

There are many different forms (eg, vial, cartridge, injection device) available for this medicine. Make sure your doctor, nurse, or pharmacist instructs you on how to prepare and administer this medication. Also, read all instructions carefully to be sure you know how to use your device.

Each time you get your medicine, check to be sure you have received the proper device. Talk to your pharmacist if you have questions about the device that you were given.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. This will help prevent skin problems from the injections.

Use a new needle, unopened vial, or syringe each time you inject your medicine.

You might not use all of the medicine in each vial (glass container). Use each vial only one time. Do not save an open vial. If the medicine in the vial has changed color, or if you see particles in it, do not use it.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For treatment of growth hormone deficiency:
    • Adults—
      • Nutropin® or Nutropin AQ®:
        • Non-weight based: At first, the usual dose is 0.15 to 0.3 milligrams (mg) injected under the skin once a day. Your doctor may adjust your dose if needed.
        • Weight-based: Dose is based on body weight and must be determined by your doctor. At first, the usual dose is not more than 0.006 milligram (mg) per kilogram (kg) of body weight injected under the skin once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 0.025 to 0.0125 mg per kg of body weight per day.
      • Saizen®: Dose is based on body weight and must be determined by your doctor. At first, the usual dose is not more than 0.005 mg per kg of body weight injected under the skin once a day. Your doctor may adjust your dose if needed.
    • Children—
      • Nutropin® or Nutropin AQ®: Dose is based on body weight and must be determined by your doctor. The weekly dose is up to 0.3 to 0.7 mg per kg of body weight injected under the skin and divided into daily doses. Your doctor may adjust your dose if needed.
      • Saizen®: Dose is based on body weight and must be determined by your doctor. The usual dose is 0.06 mg per kg of body weight, given 3 times per week and injected under the skin or into a muscle. Your doctor may adjust your dose if needed.
      .
  • For treatment of growth failure due to chronic kidney disease:
    • Children—Dose is based on body weight and must be determined by your doctor. The weekly dose is up to 0.35 milligram (mg) per kilogram (kg) of body weight injected under the skin and divided into daily doses. Your doctor may adjust your dose if needed.
  • For treatment of idiopathic short stature:
    • Children—Dose is based on body weight and must be determined by your doctor. The weekly dose is up to 0.3 milligram (mg) per kilogram (kg) of body weight injected under the skin and divided into daily doses. Your doctor may adjust your dose if needed.
  • For treatment of short bowel syndrome:
    • Adults—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 0.1 milligram (mg) per kilogram (kg) of body weight injected under the skin once a day for 4 weeks. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.
  • For treatment of short stature with Turner syndrome:
    • Children—Dose is based on body weight and must be determined by your doctor. The weekly dose is up to 0.375 milligram (mg) per kilogram (kg) of body weight injected under the skin and divided into equal doses 3 to 7 times per week. Your doctor may adjust your dose if needed.

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store unopened vials, cartridges, and injection devices of Nutropin® and Nutropin AQ® in the refrigerator, away from heat and direct light. Do not freeze.

Store unopened vials of Saizen® and Zorbtive® at room temperature, away from heat and direct light. Do not freeze.

Store the medicine that has been mixed in the refrigerator. The Nutropin® or Saizen® vials and Zorbtive® that has been mixed should be used within 14 days. The Saizen® click.easy® cartridge that has been mixed should be used within 21 days. Nutropin AQ® vial, cartridge, and injection device should be used within 28 days. Make sure you understand how long you can store the medicine after it has been mixed. Throw away any mixed medicine that has not been used within this time.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abnormal or decreased touch sensation
• bleeding after defecation
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• changes in skin color
• cold flu-like symptoms
• cold hands and feet
• confusion
• constipation
• cough or hoarseness
• darkened urine
• decreased urination
• diarrhea
• difficult urination
• dizziness
• dry mouth
• fainting or loss of consciousness
• fast heartbeat
• fast or irregular breathing
• feeling unusually cold
• fever or chills
• full or bloated feeling
• general feeling of discomfort or illness
• headache
• increase in heart rate
• itching or skin rash
• joint pain
• light-colored stools
• lightheadedness
• loss of appetite
• lower back or side pain
• muscle aching or cramping
• muscle pain or stiffness
• nausea
• pain
• pain, redness, or swelling in the arm or leg
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pressure in the stomach
• rapid, shallow breathing
• rapid weight gain
• rectal bleeding
• runny nose
• shivering
• sneezing
• sore mouth or tongue
• sore throat
• stomach bloating, burning, cramping, or pain
• sudden decrease in the amount of urine
• sweating
• swelling of the abdominal or stomach area
• swelling of the eyes or eyelids
• swelling or puffiness of the face
• swollen joints
• thirst
• tightness in the chest
• tingling of the hands or feet
• trouble breathing
• trouble sleeping
• uncomfortable swelling around the anus
• unpleasant breath odor
• unusual tiredness or weakness
• unusual weight gain or loss
• vomiting
• vomiting of blood
• white patches in the mouth, tongue, or throat
• wrinkled skin
• yellow eyes or skin

• Bone or skeletal pain
• burning, numbness, pain, or tingling in all fingers except smallest finger
• chest pain
• depressed mood
• dry skin and hair
• feeling cold
• hair loss
• hoarseness or husky voice
• slowed heartbeat
• swelling of the ankles

Get emergency help immediately if any of the following symptoms of overdose occur:

• Anxiety
• blurred vision
• changes in vision
• cold sweats
• coma
• cool, pale skin
• decrease in the amount of urine
• depression
• excessive sweating
• extreme weakness
• flushed, dry skin
• frequent urination
• fruit-like breath odor
• increase in hands and feet size
• increased hunger
• increased thirst
• increased urination
• increased volume of pale, diluted urine
• nightmares
• noisy, rattling breathing
• pain in the arms or legs
• seizures
• shakiness
• slurred speech
• stop in menstruation
• swelling of the fingers or hands
• troubled breathing at rest

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• breast pain
• change in the color, amount, or odor of vaginal discharge
• congestion
• discoloration of the fingernails or toenails
• dryness or soreness of the throat
• excess air or gas in the stomach or intestines
• frequent urge to defecate
• increased sweating
• passing gas
• sneezing
• straining while passing stool
• stuffy nose
• tender, swollen glands in neck
• trouble with swallowing
• voice changes

• Discouragement
• feeling sad or empty
• irritability
• lack of appetite
• loss of interest or pleasure
• tiredness
• trouble concentrating

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to help patients with HIV gain weight.
• It may be given to you for other reasons. Talk with the doctor.

For all patients taking this medicine:

• Tell all of your health care providers that you take Serostim. This includes your doctors, nurses, pharmacists, and dentists.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Avoid drinking alcohol while taking Serostim.
• Follow the diet and workout plan that your doctor told you about.
• If you have a history of cancer or tumors, talk with your doctor. The chance of new tumors may be raised in some patients.
• If you have Turner syndrome, talk with your doctor. The chance of ear infections, high blood pressure, and very bad blood vessel problems like stroke and bleeding in the brain may be raised.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• If you are 65 or older, use Serostim with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Children:

• Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn. Talk with the doctor to see if this product has benzyl alcohol in it.

Use Serostim as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Move the site where you give the shot with each shot.
• Do not give into skin that is irritated, bruised, red, infected, or scarred.
• Do not shake the solution.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Wash your hands before and after use.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Acute Critical Illness

Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo [see Contraindications (4)].

Concomitant Antiretroviral Therapy

In some experimental systems, somatropin has been shown to potentiate HIV replication in vitro at concentrations ranging from 50-250 ng/mL. There was no increase in virus production when the antiretroviral agents, zidovudine, didanosine or lamivudine were added to the culture medium. Additional in vitro studies have shown that somatropin does not interfere with the antiviral activity of zalcitabine or stavudine. In the controlled clinical trials, no significant somatropin-associated increase in viral burden was observed. However, the protocol required all participants to be on concomitant antiretroviral therapy for the duration of the study. In view of the potential for acceleration of virus replication, it is recommended that HIV patients be maintained on antiretroviral therapy for the duration of Serostim treatment.

Neoplasms

Because malignancies are more common in HIV positive individuals, the risks and benefits of starting somatropin in HIV positive patients should be carefully considered before initiating Serostim treatment and patients should be monitored carefully for the development of neoplasms if treatment with somatropin is initiated.

Monitor all patients with a history of any neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor [see Contraindications (4)].

Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes of preexisting nevi.

Impaired Glucose Tolerance/Diabetes

Hyperglycemia may occur in HIV infected individuals due to a variety of reasons. In wasting patients, treatment with Serostim 0.1 mg/kg daily and 0.1 mg/kg every other day for 12 weeks was associated with approximately 10 mg/dL and 6 mg/dL increases in mean fasting blood glucose concentrations, respectively. The increases occurred early in treatment. Patients with other risk factors for glucose intolerance should be monitored closely during Serostim therapy.

During safety surveillance of patients with HIV-associated wasting, cases of new onset impaired glucose tolerance, new onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving Serostim. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when Serostim was discontinued, while in others, the glucose intolerance persisted. Some of these patients required initiation or adjustment of antidiabetic treatment while on Serostim.

In clinical trials of Serostim conducted in HIV patients with lipodystrophy (an unapproved indication), evidence of dose-dependent glucose intolerance and related adverse reaction was observed at doses of 4 mg Serostim daily and 4 mg Serostim every other day for 12 weeks [see Adverse Reactions (6.1)].

Intracranial Hypertension

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose. Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved.

Severe Hypersensitivity

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4)].

Fluid Retention/Carpal Tunnel Syndrome

Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Serostim, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing [see Dosage and Administration (2.1)].

Carpal tunnel syndrome may occur during treatment with Serostim. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the weekly number of doses of Serostim, it is recommended that treatment be discontinued.

Lipoatrophy

When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.2)].

Pancreatitis

Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin-treated patient, especially a child who develops abdominal pain.

Pregnancy

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits. Doses up to 5 to 10 times the human dose, based on body surface area, have revealed no evidence of impaired fertility or harm to the fetus due to Serostim. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Serostim should be used during pregnancy only if clearly needed.

Nursing Women

It is not known whether Serostim is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Serostim is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients with HIV have not been established. Available evidence suggests that somatropin clearance is similar in adults and children, but no pharmacokinetic studies have been conducted in children with HIV.

In two small studies, 11 children with HIV-associated failure to thrive were treated subcutaneously with human growth hormone. In one study, five children (age range, 6 to 17 years) were treated with 0.04 mg/kg/day for 26 weeks. In a second study, six children (age range, 8 to 14 years) were treated with 0.07 mg/kg/day for 4 weeks. Treatment appeared to be well tolerated in both studies. The preliminary data collected on a limited number of patients with HIV-associated failure to thrive appear to be consistent with safety observations in growth hormone-treated adults with HIV wasting.

Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The "gasping syndrome," (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

Geriatric Use

Clinical studies with Serostim did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may be more sensitive to the action of somatropin, and therefore, may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments should be considered for older patients [see Dosage and Administration (2)].

Hepatic Impairment

No studies have been conducted for Serostim in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

Renal Impairment

Subjects with chronic renal failure tend to have decreased somatropin clearance compared to those with normal renal function. However, no studies have been conducted for Serostim in patients with renal impairment [see Clinical Pharmacology (12.3)].

Gender Effect

Biomedical literature indicates that a gender-related difference in the mean clearance of r-hGH could exist (clearance of r-hGH in males > clearance of r-hGH in females). However, no gender-based analysis is available for Serostim in normal volunteers or patients infected with HIV.

Serostim is a human growth hormone (hGH) produced by recombinant DNA technology. Serostim has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary growth hormone. Serostim is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. Serostim is secreted directly through the cell membrane into the cell-culture medium for collection and purification.

Serostim is a sterile lyophilized powder intended for subcutaneous injection after reconstitution to its liquid form.

Vials of Serostim contain either 4 mg, 5 mg, or 6 mg. Each vial contains the following:

Each 4 mg multi-vial is supplied in a combination package with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol). The pH is adjusted with sodium hydroxide of phosphoric acid to give a pH of 7.4 to 8.5 after reconstitution.

Each 5 mg single-use vial is supplied in a combination package with Sterile Water for Injection, USP. The pH is adjusted with sodium hydroxide or phosphoric acid to give a pH of 6.5 to 8.5 after reconstitution.

Each 6 mg single-use vial is supplied in a combination package with Sterile Water for Injection, USP. The pH is adjusted with sodium hydroxide of phosphoric acid to give a pH of 7.4 to 8.5 after reconstitution.

HIV-Associated Wasting or Cachexia

The clinical efficacy of Serostim in HIV-associated wasting or cachexia was assessed in two placebo-controlled trials. All study subjects received concomitant antiretroviral therapy. There was no increase in the incidence of Kaposi's sarcoma (KS), lymphoma, or in the progression of cutaneous Kaposi's sarcoma in clinical studies of Serostim. Patients with internal KS lesions were excluded from the studies. Potential effects on other malignancies are unknown.

Clinical Trial 1:

A 12-week, randomized, double-blind, placebo-controlled study followed by an open-label extension phase enrolled 178 patients with severe HIV wasting taking nucleoside analogue therapy (pre-HAART era). The primary endpoint was body weight. Body composition was assessed using dual energy X-ray absorptiometry (DXA) and physical function was assessed by treadmill exercise testing. Patients meeting the inclusion/exclusion criteria were treated with either placebo or Serostim 0.1 mg/kg daily. Ninety-six percent (96%) were male. The average baseline CD4 count/microliter was 85. The results from one hundred forty (140) evaluable patients were analyzed (those completing the 12-week course of treatment and who were at least 80% compliant with study drug). After 12 weeks of therapy, the mean difference in weight increase between the Serostim-treated group and the placebo-treated group was 1.6 kg (3.5 lb). Mean difference in lean body mass (LBM) change between the Serostim-treated group and the placebo-treated group was 3.1 kg (6.8 lbs) as measured by DXA. Mean increase in weight and LBM, and mean decrease in body fat, were significantly greater in the Serostim-treated group than in the placebo group (p=0.011, p<0.001, p<0.001, respectively) after 12 weeks of treatment (Figure 1). There were no significant changes with continued treatment beyond 12 weeks suggesting that the original gains of weight and LBM were maintained (Figure 1).

Treatment with Serostim resulted in a significant increase in physical function as assessed by treadmill exercise testing. The median treadmill work output increased by 13% (p=0.039) at 12 weeks in the group receiving Serostim (Figure 2). There was no improvement in the placebo-treated group at 12 weeks. Changes in treadmill performance were significantly correlated with changes in LBM.

Figure 1: Mean Changes in Body Composition

Figure 2: Median Treadmill Work Output

Clinical Trial 2:

A 12-week, randomized, double-blind, placebo-controlled study enrolled 757 patients with HIV-associated wasting, or cachexia. The primary efficacy endpoint was physical function as measured by cycle ergometry work output. Body composition was assessed using bioelectrical impedance spectroscopy (BIS) and also by dual energy X-ray absorptiometry (DXA) at a subset of centers. Patients meeting the inclusion/exclusion criteria were treated with either placebo, approximately 0.1 mg/kg every other day (qod) of Serostim, or approximately 0.1 mg/kg daily at bedtime of Serostim. All results were analyzed in intent-to-treat populations (for cycle ergometry work output, n=670). Ninety-one percent (91%) were male and 88% were on HAART anti-retroviral therapy. The average baseline CD4 count/µL was 446. Six hundred forty-six patients (646) completed the 12-week study and continued in the Serostim treatment extension phase of the trial.

Clinical Trial 2 results are summarized in Tables 4 and 5:

The mean maximum cycle work output until exhaustion increased after 12 weeks by 2.57 kilojoules (kJ) in the Serostim 0.1 mg/kg daily group (p<0.01) and by 2.53 kJ in the Serostim 0.1 mg/kg every other day group (p<0.01) compared with placebo (Table 4). Cycle work output improved approximately 9% in both active treatment arms and decreased <1% in the placebo group. Lean body mass (LBM) and body weight (BW) increased, and fat mass decreased, in a dose-related fashion after treatment with Serostimand placebo (Table 5). The LBM results obtained by BIS were confirmed with DXA.

Patients' perceptions of the impact of 12 weeks of treatment on their wasting symptoms as assessed by the Bristol-Meyers Anorexia/Cachexia Recovery Instrument improved with both doses of Serostimin Clinical Trial 2.

Extension Phase: All patients (n=646) completing the 12-week placebo-controlled phase of Clinical Trial 2 continued Serostim treatment into an extension phase. Five hundred and forty eight of these patients completed an additional 12 weeks of active treatment. In these patients, changes in cycle ergometry work output, LBM, BW, and fat mass either improved further or were maintained with continued Serostim treatment.