Comparison of Injection Site Pain Experience for Semaglutide and Dulaglutide sc

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04189848
• Collaborator: (none)
• Enrollment: 104
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.8
• Patients Per Site Per Month: 36.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers; Diabetes Mellitus, Type 2; Overweight; Obesity	Drug: Semaglutide; Drug: Dulaglutide	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Trial to Complare the Injection Site Pain Experience of Semaglutide 0.25 mg and Dulaglutide 0.75 mg Administered sc
• Actual Study Start Date: Dec 3, 2019
• Actual Primary Completion Date: Jan 29, 2020
• Actual Study Completion Date: Feb 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide followed by dulaglutide The 2 treatments will be administered at least 30 minutes apart, one in each side of the stomach	Drug: Semaglutide; Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.; Drug: Dulaglutide; Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.
Experimental: Dulaglutide followed by semaglutide The 2 treatments will be administered at least 30 minutes apart, one in each side of the stomach	Drug: Semaglutide; Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.; Drug: Dulaglutide; Subjects will receive 1 dose of semaglutide 0.25 mg and 1 dose of dulaglutide 0.75 mg on the same day.

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Groningen		Netherlands	9728 NZ

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Oct 6, 2020
• Statistical Analysis Plan - Oct 6, 2020

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04189848
• Other Study ID Numbers: NN9535-4648; 2019-83003844-57; U1111-1241-0348
• First Posted: Dec 6, 2019
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Overweight; Dulaglutide

Study Results

Participant Flow

Recruitment Details	The trial was conducted at one site in the Netherlands.
Pre-assignment Detail	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.

Arm/Group Title	Sequence A: Semaglutide (Right) Then Dulaglutide (Left)	Sequence B: Semaglutide (Left) Then Dulaglutide (Right)	Sequence C: Dulaglutide (Right) Then Semaglutide (Left)	Sequence D: Dulaglutide (Left) Then Semaglutide (Right)
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of 0.25 milligrams (mg) of semaglutide on the right side of abdomen (in treatment period 1); followed by an s.c. injection of 0.75 mg of dulaglutide product on the left side of abdomen (in treatment period 2). The 2 products were administered on the same day (Day 1) with at least 30 minutes apart from each other.	Participants were to receive an s.c. injection of 0.25 mg of semaglutide on the left side of abdomen (in treatment period 1); followed by an s.c. injection of 0.75 mg of dulaglutide on the right side of abdomen (in treatment period 2). The 2 products were administered on the same day (Day 1) with at least 30 minutes apart from each other.	Participants were to receive an s.c. injection of 0.75 mg of dulaglutide on the right side of abdomen (in treatment period 1); followed by an s.c. injection of 0.25 mg of semaglutide on the left side of abdomen (in treatment period 2). The 2 products were administered on the same day (Day 1) with at least 30 minutes apart from each other.	Participants were to receive an s.c. injection of 0.75 mg of dulaglutide on the left side of abdomen (in treatment period 1); followed by an s.c. injection of 0.25 mg of semaglutide on the right side of abdomen (in treatment period 2). The 2 products were administered on the same day (Day 1) with at least 30 minutes apart from each other.
Period Title: Treatment Period 1 (Day 1)
STARTED	26	26	25	27
COMPLETED	26	26	25	27
NOT COMPLETED	0	0	0	0
Period Title: Treatment Period 1 (Day 1)
STARTED	26	26	25	27
COMPLETED	26	26	25	27
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	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.
Overall Participants	104
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.9 (17.5)
Sex: Female, Male (Count of Participants)
Female	62 59.6%
Male	42 40.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	104 100%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White + Black or African	5 4.8%
Asian	3 2.9%
Black or African American	1 1%
White	94 90.4%
White + Asian	1 1%

Outcome Measures

1. Primary Outcome

Title	Intensity of Injection Site Pain
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Semaglutide	Dulaglutide
Arm/Group Description	Participants were to receive an s.c. injection of 0.25 mg of semaglutide on either (left or right) sides of abdomen in any of the sequences A/B/C/D on Day 1.	Participants were to receive an s.c. injection of 0.75 mg of dulaglutide on either (left or right) sides of abdomen in any of the sequences A/B/C/D on Day 1.
Measure Participants	104	104
Mean (Standard Deviation) [Score on a scale]	5.6 (10.1)	11.5 (12.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide, Dulaglutide
	Comments	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.
	Type of Statistical Test	Other
	Comments	Treatment comparison
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -8.2 to -3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Day 1 to Day 28. Results are based on the safety analysis set which included all participants who had received at least 1 injection of semaglutide or dulaglutide (included any skin contact with trial product whether the injection was completed or not).
Adverse Event Reporting Description	All presented adverse events are treatment emergent adverse events (TEAEs). TEAE was defined as an event that had onset date on or after the day of first injection and no later than 28 days after the day of last injection. The trial was crossover and injections were given only 30 minutes apart. Therefore it was not possible to say which product the AE was related to. Hence, AE data are presented for the overall study.
Arm/Group Title	Overall Study
Arm/Group Description	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.
All Cause Mortality
	Overall Study
	Affected / at Risk (%)	# Events
Total	0/104 (0%)
Serious Adverse Events
	Overall Study
	Affected / at Risk (%)	# Events
Total	0/104 (0%)
Other (Not Including Serious) Adverse Events
	Overall Study
	Affected / at Risk (%)	# Events
Total	34/104 (32.7%)
Gastrointestinal disorders
Nausea	22/104 (21.2%)	23
Metabolism and nutrition disorders
Decreased Appetite	12/104 (11.5%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.