Acromegaly
Conditions
Brief summary
The study is designed to investigate the safety, tolerability and efficacy of DG3173 in untreated acromegaly patients. Twenty patients received ascending single doses of DG3173 and one dose of octreotide, the current gold standard of medical therapy for acromegaly, with each patient receiving all doses of DG3173 as well as octreotide.
Interventions
DRUGoctreotide
Eligible patients are to receive 300 µg octreotide as active comparator, followed by four ascending doses of 100 µg, 300 µg, 900 µg and 1800 µg DG3173. All treatments will be administered consecutively to all patients as single subcutaneous bolus injections.
DRUGDG3173
Eligible patients are to receive 300 µg octreotide as active comparator, followed by four ascending doses of 100 µg, 300 µg, 900 µg and 1800 µg DG3173. All treatments will be administered consecutively to all patients as single subcutaneous bolus injections.
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 childbearing potential or women of child bearing potential who either abstain from sexual intercourse, have a sterile partner or practice a medically approved double barrier method of contraception * Diagnosis of acromegaly of pituitary origin * Have age adjusted Insulin like Growth Factor 1 (IGF-1) concentrations ≥1.5 times the upper limit of normal range on two consecutive measurements in the 6 months prior to the first dosing day (including the measurement to be made at screening \[Visit 2\]) * Have a random hGH level of ≥5 µg/L in the 6 months prior to or at screening (Visit 2) * Have given written informed consent * Ability to comply with the requirements of the protocol of the study
Exclusion criteria
* Previous specific treatment for acromegaly in the 6 months prior to screening (Visit 2), including somatostatin analogues (SSAs), surgery, radiotherapy and pegvisomant * Treatment with dopamine agonists in the 3 months prior to screening (Visit 2) * Uncontrolled hypertension or orthostatic hypotension * 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 (Visit 2) * Receipt of blood, blood products or plasma derivatives 60 days prior to screening (Visit 2) * Pregnancy or lactation * 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 * Any clinically significant abnormal 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 |
|---|---|
| Participants With Trough Human Growth Hormone < 2.5 ug/mL | Pre dose and 0.33, 0.67 hours and 1, 1.5, 2, 3, 4, 5, 6 and 8 hours post dose on each dosing day. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cross-over Interventions: octreotide and DG3173. Eligible patients are to receive 300 µg octreotide as active comparator, followed by four ascending doses of 100 µg, 300 µg, 900 µg and 1800 µg DG3173. All treatments will be administered consecutively to all patients as single subcutaneous bolus injections. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Cross-over |
|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment Ukraine | 20 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 2 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 / 20 | 0 / 20 | 1 / 20 | 0 / 19 | 1 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Participants With Trough Human Growth Hormone < 2.5 ug/mL
Time frame: Pre dose and 0.33, 0.67 hours and 1, 1.5, 2, 3, 4, 5, 6 and 8 hours post dose on each dosing day.
Population: Baseline: an 8 hour untreated human growth hormone (hGH) profile was obtained in the period between 15 and 7 days prior to the first study treatment administration.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Baseline (Untreated Control) | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 1 participants with trough hGH < 2.5 µg/mL |
| 300 µg Octreotide | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 8 participants with trough hGH < 2.5 µg/mL |
| 100 µg DG3173 | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 4 participants with trough hGH < 2.5 µg/mL |
| 300 µg DG3173 | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 6 participants with trough hGH < 2.5 µg/mL |
| 900 µg DG3173 | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 7 participants with trough hGH < 2.5 µg/mL |
| 1800 µg DG3173 | Participants With Trough Human Growth Hormone < 2.5 ug/mL | 8 participants with trough hGH < 2.5 µg/mL |