This was a 6-month, single-arm, open-label, multicenter study evaluating the efficacy and safety of self- or partner-administration of lanreotide in patients with acromegaly. Patients either switched directly from octreotide LAR (switch patients) or were SSA treatment naïve or not currently on octreotide (“other” patients; they could have had octreotide >4 months prior to enrollment). Patients receiving dopamine agonist (DA) treatment before the study were maintained on the same DA dose.
After screening, patients were evaluated at baseline (week 0) and at weeks 4, 12 and 24. There was an additional 30-day safety follow-up after the last lanreotide injection at week 24. Patients received deep subcutaneous injections of lanreotide every 28 days. Switch patients were started either on 90 or 120 mg lanreotide, depending on their prior treatment regimen (e.g., typically 90 mg if they were on 20 mg octreotide LAR and 120 mg if they were on 30 mg octreotide LAR). All “other” patients were started on 90 mg lanreotide except for one patient, who was on a DA and had previously been on 30 mg octreotide LAR >4 months prior to enrollment, who started on 120 mg lanreotide. The dose was adjusted to 60, 90 or 120 mg at week 16 based on the patient’s symptoms and IGF-1 levels at week 12. A schematic illustration of the study design is shown in Fig. .
Schematic representation of the study design
Patients were given the choice to self- or partner-inject lanreotide. A “partner” was defined as any person whom the patient trusted to administer the injection. The local health care professional demonstrated the injection technique at week 0 to either the patient or the partner, but the patient or partner administered all the injections.
Health care professionals completed a questionnaire assessing the competency of each patient/partner at weeks 0, 4, 8 (if needed) and 24. The competency questionnaire included questions such as whether or not the patient/partner followed the instructions given, administered the injection correctly, administered the complete dose, inserted the needle correctly and inserted the needle to the appropriate depth. Patients completed a questionnaire inquiring about acromegaly symptoms at weeks 0, 12, and 24 and an injection diary after each injection. A total score for symptoms was calculated at each visit based on the patient’s sweating, snoring, joint pain, headache and fatigue. Each symptom was scored as −2 (always), −1 (most of the time), 0 (sometimes), 1 (rarely) or 2 (never). Switch patients also completed a convenience questionnaire at weeks 0 and 24. All questionnaires were made available in English and Spanish.
The primary endpoint was the percentage of patients/partners competent to self- or partner-administer lanreotide at study completion as assessed by the health care professional. Secondary assessments included IGF-1 and glucose-suppressed GH levels, symptom and convenience questionnaires and safety assessments. Safety assessments included a physical examination, collection of adverse events (AEs) and laboratory examinations such as a complete blood count (CBC), serum chemistries, thyroid function tests and urinalysis.
Fifty-nine patients with acromegaly were recruited by the local investigators and studied at one of thirteen centers in the United States. The study protocol was approved by the local institutional review board of participating centers (see additional details at: www.clinicaltrials.gov
; identified: NCT00447499). Informed consent was obtained from the patients and their partners prior to any study-related activities.
The study inclusion criteria included suitably motivated patients with a clinical diagnosis of acromegaly due to a pituitary tumor and age ≥18 years. Switch patients also had to have taken a constant dose of octreotide LAR for at least 3 months, with serum IGF-1 no higher than 10% above normal. Switch patients had to have their last octreotide LAR injection 28–35 days prior to study enrollment. The study exclusion criteria included pituitary surgery within 3 months of screening, pituitary radiation therapy within 3 years of screening, GH receptor antagonist therapy within 6 months of screening, current octreotide LAR dose >30 mg every 28 days, renal or hepatic abnormalities, symptomatic cholelithiasis, poorly controlled diabetes or thyroid disease, pregnancy or breastfeeding. Contraception was mandatory in patients of child-bearing potential.
IGF-1 and GH assays
Serum IGF-1 levels were measured with a radioimmunoassay after acid-alcohol extraction (RIA-AE) via gamma counter (Esoterix; Calabasas Hills, CA). The intra-assay variability of the RIA-AE assay, measured by the coefficient of variation (CV), was 5–14% based on four samples and five assay runs of each sample. The inter-assay variability of the RIA-AE assay was 7–17% based on four samples and three assay runs of each sample.
Serum GH levels were measured with an immunochemiluminometric assay (ICMA) using an immunometer (Esoterix; Calabasas Hills, CA). The intra-assay variability of the ICMA assay, measured by the CV, was 4–14% based on ten samples and four assay runs of each sample. The inter-assay variability of the ICMA assay was 7–14% based on six samples and seventeen assay runs of each sample.
For the baseline characteristics, frequency counts and percents (%) were calculated for sex, previous pituitary surgery, prior acromegaly medication, SSA treatment and DA treatment. Mean and standard deviation (SD) were calculated for age, body mass index (BMI), duration of acromegaly, time since last pituitary surgery and time since last SSA treatment. The comparisons between switch and “other” patients were performed using either a chi-square test or Student’s t-test.
The number and percent of patients who correctly administered the lanreotide injection at week 24 were calculated based on the competency questionnaire completed by the health care professionals for each patient/partner. For the switch patients, the number and percent of patients who experienced pain (i.e., not painful, somewhat painful, moderately painful and very painful) from the lanreotide injection at week 24 and from the octreotide LAR injection at week 0 were calculated based on the convenience questionnaire completed by the switch patients. The pain experience (not painful) for the two treatments was compared using a McNemar’s test. For the preference for future treatment, the number and percent of switch patients who preferred lanreotide or octreotide LAR or who had no preference at week 24 or early termination were calculated based on the convenience questionnaire completed by the switch patients. A chi-square test was used to test the hypothesis that more than 50% of switch patients would prefer one drug over the other for future use.
The biochemical control of glucose-suppressed GH and IGF-1 were determined at weeks 0 and 24 as: normal IGF-1 and GH <1 μg/L; normal IGF-1 only; GH <1 μg/L only or none of the above. For each of these four categories, the number and percent of patients were calculated for switch and “other” patients. A McNemar’s test was used to test the change from weeks 0 to 24 within each of the two the groups. No between group comparisons were performed because the switch patients had been taking octreotide LAR for ≥3 months prior to study enrollment and their serum IGF-1 levels were no higher than 10% above normal.
Acromegaly symptoms scores were categorized as symptoms present (scores of −2 to 0) or absent (scores of 1 or 2), and the total score was used to evaluate symptom control in each patient at weeks 0 and 24. A McNemar’s test was used to test the change in symptom status from week 0 to week 24 or early termination within each of the two the groups using the total score.
AEs were coded using the MedDRA dictionary Version 8.1. Possibly and probably treatment-related AEs occurring in more than 5% of patients were summarized for switch and “other” patients. A chi-square test was used to compare the two groups.