Diabetes Mellitus, Type 2, Healthy Volunteers, Obesity, Overweight
Conditions
Brief summary
This study in healthy men and women looks at the injection site experience of semaglutide and dulaglutide given subcutaneously (s.c., under the skin). Participants will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day. The 2 injections will be given at least 30 minutes apart, one in each side of the stomach. Participants will be in the clinic research center for 1 day. A follow-up phone call will take place between 4 and 5 weeks after the injections were given.
Interventions
DRUGSemaglutide
Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.
DRUGDulaglutide
Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent. * Body mass index equal to or above 25.0 kg/m\^2. * Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the Investigator.
Exclusion criteria
* Known or suspected hypersensitivity to trial product(s) or related products. * Previous participation in trial INS-4603, INS-4582 or NN9535-4648. Participation is defined as having received investigational product. * Female who is pregnant, breast-feeding or intends to become pregnant within 4 weeks of Day 1 or is of childbearing potential and not using highly effective contraceptive methods. * Participation in a drug study within 60 days prior to drug administration in the current trial OR participation in more than 4 other drug studies in the 12 months prior to drug administration in the current trial. * Any disorder which in the Investigator's opinion might jeopardise subject's safety, evaluation of results, or compliance with the protocol. * Glycosylated haemoglobin (HbA1c) equal to or above 6.5 % (48 mmol/mol) at screening. * Supine blood pressure at screening (after resting for 5 minutes or longer) outside the range of 90-160 mmHg for systolic or 45-89 mmHg for diastolic. * Supine pulse rate (as part of vital signs) outside the range of 40-100 beats/min after resting for 5 minutes or longer at screening. * Use of prescription medicinal products or non-prescription drugs or herbal products, except routine vitamins, topical medication, contraceptives and occasional use of paracetamol (not allowed within 24 hours prior to drug administration), within 14 days prior to Day 1. * Diagnostic test results positive for HIV-1 or HIV-2 infection. * Diagnostic test results positive for active hepatitis B or hepatitis C infection. * Mental incapacity, language barriers, or unwillingness to comply with the requirements of the protocol, which may preclude adequate understanding or cooperation during the trial as judged by the Investigator. * Average intake of more than 21 units of alcohol per week for male subjects and more than 14 units per week for female subjects: 1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits). * Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines \[including ecstasy\], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at screening and admission to the clinical research centre. * Use of tobacco and nicotine products, defined as any of the below: * Smoking more than 1 cigarette or the equivalent per day on average. * Not able or willing to refrain from smoking and use of nicotine substitute products during the in-house period. * Blood donation, plasma donation, or blood draw * In excess of 400 mL within the past 90 days prior to the day of screening * In excess of 50 mL within the past 30 days prior to the day of screening * Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. * Subjects with a history of malignant neoplasms within the past 5 years prior to screening will be excluded from the trial. * Presence or history of pancreatitis (acute or chronic; as declared by the subject or reported in the medical records). * Subject is not able to understand and read English or Dutch, or subject is not able to understand and comply with the trial requirements. * Subject depends on the Sponsor, the Investigator, or the study centre, or subject is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the trial. * Vulnerable subject (e.g. person kept in detention) who may have an increased likelihood of being wronged or of incurring additional harm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intensity of Injection Site Pain | 1 minute after each injection (Day 1) | The intensity of injection site pain was measured on a visual analogue scale (VAS). The VAS consists of a horizontal 100 millimeters (mm) line where 0 mm corresponded to no pain and 100 mm corresponded to unbearable pain. After each injection, the participants rated their pain perception at the VAS by marking a vertical line across the 100 mm horizontal line. The distance (mm) between the endpoint no pain and the vertical line on the VAS was recorded and analysed. |
Countries
Netherlands
Participant flow
Recruitment details
The trial was conducted at one site in the Netherlands.
Pre-assignment details
Participants were randomised in a 2×2 scheme evenly to 4 sequences (A, B, C and D) of semaglutide product (Semaglutide 1.34 mg/mL PDS290 pre-filled pen-injector) or dulaglutide product (Trulicity 0.75 mg solution for injection in pre-filled pen) and side of injection (right/left) on abdomen.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants were to receive s.c. injections of 0.25 mg semaglutide and 0.75 mg dulaglutide each from any of the sequences A/B/C/D on Day 1. The 2 products were administered at least 30 minutes apart from each other. | 104 |
| Total | 104 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 36.9 years STANDARD_DEVIATION 17.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants |
| Race/Ethnicity, Customized Race White | 94 Participants |
| Race/Ethnicity, Customized Race White + Asian | 1 Participants |
| Race/Ethnicity, Customized Race White + Black or African | 5 Participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 104 |
| other Total, other adverse events | 34 / 104 |
| serious Total, serious adverse events | 0 / 104 |
Outcome results
Primary
Intensity of Injection Site Pain
The intensity of injection site pain was measured on a visual analogue scale (VAS). The VAS consists of a horizontal 100 millimeters (mm) line where 0 mm corresponded to no pain and 100 mm corresponded to unbearable pain. After each injection, the participants rated their pain perception at the VAS by marking a vertical line across the 100 mm horizontal line. The distance (mm) between the endpoint no pain and the vertical line on the VAS was recorded and analysed.
Time frame: 1 minute after each injection (Day 1)
Population: The per protocol (PP) set included all participants who had received both injections of semaglutide and dulaglutide and had completed both intensity of injection site pain assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Intensity of Injection Site Pain | 5.6 Score on a scale | Standard Deviation 10.1 |
| Dulaglutide | Intensity of Injection Site Pain | 11.5 Score on a scale | Standard Deviation 12.8 |
Comparison: Intensity of injection site pain was analysed by a fixed analysis of variance model with VAS pain score as the dependent variable, and product, injection side (right side, left side), injection number (first injection, second injection), and participant as fixed effects.p-value: <0.000195% CI: [-8.2, -3.6]ANOVA