Acromegaly
Conditions
Brief summary
This study is designed to assess the effect of the different continuous s.c. infusion treatments on the human growth hormone (hGH) levels in untreated acromegalic patients in comparison to a standard dose of octreotide. In addition, the pharmacokinetic profile and the safety and tolerability of DG3173 after continuous s.c. infusion will be evaluated.
Interventions
DRUGsaline
Eligible patients are to receive a constant 23 hour subcutaneous infusion of saline as placebo comparator and will be randomized in an equal ratio to one of three treatment sequences of doses of 920, 2760 and 5520 µg DG3173 by constant 23 hour subcutaneous infusions in a random sequence followed by three subcutaneous injections of 300 µg octreotide at approximately 8 hour intervals as an active comparator.
DRUGDG3173
Eligible patients are to receive a constant 23 hour subcutaneous infusion of saline as placebo comparator and will be randomized in an equal ratio to one of three treatment sequences of doses of 920, 2760 and 5520 µg DG3173 by constant 23 hour subcutaneous infusions in a random sequence followed by three subcutaneous injections of 300 µg octreotide at approximately 8 hour intervals as an active comparator.
DRUGoctreotide
Eligible patients are to receive a constant 23 hour subcutaneous infusion of saline as placebo comparator and will be randomized in an equal ratio to one of three treatment sequences of doses of 920, 2760 and 5520 µg DG3173 by constant 23 hour subcutaneous infusions in a random sequence followed by three subcutaneous injections of 300 µg octreotide at approximately 8 hour intervals as an active comparator.
Sponsors
Aspireo Pharmaceuticals Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men, women of non child-bearing potential, or women of child-bearing potential who either abstain from sexual intercourse, have a sterile partner or practice two medically approved, non-hormonal methods of contraception * Diagnosis of acromegaly of pituitary origin * Have an age-adjusted insulin-like growth factor type 1 (IGF-1) concentration ≥1.2 times the upper limit of normal range on at least one measurement in the 12 months prior to screening (Visit 1) AND a second raised value screening * Have at least one random hGH level of ≥5 μg/L in the 12 months prior to screening AND a second raised value at screening * Have given written informed consent * Ability to comply with the requirements of the protocol for the study
Exclusion criteria
* Previous specific treatment for acromegaly in the 12 months prior to screening, including somatostatin analogues (SSAs); surgery; radiotherapy and pegvisomant * Treatment with dopamine agonists in the 3 months prior to screening * Uncontrolled hypertension * Type I diabetes mellitus, poorly-controlled type II diabetes mellitus (glycosylated haemoglobin \[HbA1c\] ≥7.5%) and patients requiring insulin treatment * Gallstones or gravel that could cause biliary obstruction * Hyperprolactinaemia * Participation in a clinical study within 60 days prior to screening * Receipt of blood, blood products or plasma derivatives 60 days prior to screening * Body mass index (BMI) below 22 or above 37 kg/m2 * Pregnancy, lactation or use of any hormonal based contraceptives * Concomitant intake of corticosteroids or levodopa * A history of active alcohol abuse or drug addiction * Positive viral serology screening result for hepatitis B surface antigen, antibodies to hepatitis C virus, or human immunodeficiency virus type 1 and 2 * Evidence or suspicion of tumour expansion * Clinically significant abnormality in screening ECG in the opinion of the Investigator * Any clinically significant abnormal in screening laboratory safety test (biochemistry, haematology and dipstick urinalysis) in the opinion of the Investigator * Any disease which in the Investigator's opinion would exclude the patient from the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 23 hours following each treatment |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Saline, Then DG3173, Then Octreotide Interventions: saline, DG3173 and octreotide. Eligible patients are to receive a constant 23 hour subcutaneous infusion of saline as placebo comparator and will be randomized in an equal ratio to one of three treatment sequences of doses of 920, 2760 and 5520 µg DG3173 by constant 23 hour subcutaneous infusions in a random sequence followed by three subcutaneous injections of 300 µg octreotide at approximately 8 hour intervals as an active comparator. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Saline, Then DG3173, Then Octreotide |
|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment Ukraine | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 1 / 8 | 2 / 8 | 2 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment.
Time frame: 23 hours following each treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Saline (Control) | The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 0 participants with trough hGH < 2.5 µg/mL |
| 920 µg DG3173 | The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 1 participants with trough hGH < 2.5 µg/mL |
| 2760 µg DG3173 | The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 2 participants with trough hGH < 2.5 µg/mL |
| 5520 µg DG3173 | The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 3 participants with trough hGH < 2.5 µg/mL |
| Active Control (Octreotide) | The Number of Patients Who Achieve a Trough Human Growth Hormone (hGH) Concentration of <2.5µg/L During the Last 12 Hours of the 23 Hour Profile Following Each Study Treatment. | 4 participants with trough hGH < 2.5 µg/mL |