Trial Outcomes & Findings for Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis (NCT NCT02357420)

Last Updated: 2019-07-24

Results Overview

Vomiting episodes were assessed via the Diabetic Gastroparesis Symptoms Severity Diary (DGSSD). The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of Diabetic Gastroparesis (DG) (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Each day, the participant recorded the number of vomiting episodes in the past 24 hours in the diary. Higher scores indicate more vomiting episodes. Weekly scores were averaged across the 12 weeks period. A negative change from Baseline indicates improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

393 participants

Primary outcome timeframe

7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Results posted on

2019-07-24

Participant Flow

A total 393 participants were randomized and received study treatment, and 334 participants completed the study. Five participants who received study drug but discontinued prematurely were summarized as completing the study because they fulfilled the Visit 8 (Week 12) assessments as per protocol.

Participant milestones

Participant milestones
Measure	Placebo Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Overall Study STARTED	104	98	109	82
Overall Study Full Analysis Set (FAS)	104	98	109	81
Overall Study COMPLETED	92	86	93	63
Overall Study NOT COMPLETED	12	12	16	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Overall Study Adverse Event	3	3	8	9
Overall Study Investigator Decision	1	0	0	0
Overall Study Prohibited Medication	1	1	0	0
Overall Study Protocol Non-compliance	0	0	0	1
Overall Study Withdrawn Consent	4	8	6	6
Overall Study Lost to Follow-up	3	0	2	3

Baseline Characteristics

Safety and Efficacy of Relamorelin Administered to Participants With Vomiting Symptoms and Moderate to Severe Diabetic Gastroparesis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=104 Participants Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg n=98 Participants Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg n=109 Participants Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg n=82 Participants Relamorelin 100 μg was administered SC by injection BID for 12 weeks.	Total n=393 Participants Total of all reporting groups
Age, Continuous	55.7 years STANDARD_DEVIATION 11.9 • n=93 Participants	59.3 years STANDARD_DEVIATION 10.2 • n=4 Participants	56.0 years STANDARD_DEVIATION 11.7 • n=27 Participants	57.1 years STANDARD_DEVIATION 11.0 • n=483 Participants	57.0 years STANDARD_DEVIATION 11.3 • n=36 Participants
Sex: Female, Male Female	64 Participants n=93 Participants	59 Participants n=4 Participants	65 Participants n=27 Participants	57 Participants n=483 Participants	245 Participants n=36 Participants
Sex: Female, Male Male	40 Participants n=93 Participants	39 Participants n=4 Participants	44 Participants n=27 Participants	25 Participants n=483 Participants	148 Participants n=36 Participants

PRIMARY outcome

Timeframe: 7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study treatment and provided at least 1 postbaseline primary efficacy measurement (DGSSD). Number analyzed is the number of participants with data available at the given time-point.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg n=98 Participants Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg n=109 Participants Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg n=81 Participants Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Change From Baseline to Week 12 in Weekly Vomiting Episodes Baseline	5.7 vomiting episodes per week Standard Deviation 6.0	7.7 vomiting episodes per week Standard Deviation 17.2	6.9 vomiting episodes per week Standard Deviation 10.3	4.8 vomiting episodes per week Standard Deviation 5.2
Change From Baseline to Week 12 in Weekly Vomiting Episodes Change from Baseline to Week 12	-2.9 vomiting episodes per week Standard Deviation 5.8	-3.7 vomiting episodes per week Standard Deviation 12.5	-3.8 vomiting episodes per week Standard Deviation 7.6	-1.1 vomiting episodes per week Standard Deviation 13.5

SECONDARY outcome

Timeframe: 7 days prior to Day 1 for Baseline to 7 days prior to Week 12

Population: FAS included all randomized participants who received at least 1 dose of study treatment and provided at least 1 postbaseline primary efficacy measurement (DGSSD). Number analyzed is the number of participants with data available at the given time-point.

The DGSSD is a 7-item, participant-reported daily diary designed to assess the severity of 6 core signs and symptoms of DG (nausea, abdominal pain, postprandial fullness, bloating, vomiting, and early satiety) and the frequency of vomiting episodes. Severity of nausea, bloating and abdominal pain, were assessed on a numerical rating scale of 0 to 10, with 0 equating to "no" (symptom) and 10 equating to "worst possible" (symptom). Early satiety was assessed on a 5-item scale with 1 being "Only 1 or 2 bites" and 5 being "All of a normal-sized meal"; symptom severity scores for this item were reversed and normalized to a range 0 to 10 for the development of the DGSSD 4-symptom Composite Score. The DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal pain) range is 0 to 40. Higher scores indicate worse condition. Weekly scores were averaged across 12 weeks period. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg n=98 Participants Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg n=109 Participants Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg n=81 Participants Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain) Baseline	21.4 score on a scale Standard Deviation 6.7	21.8 score on a scale Standard Deviation 6.9	21.1 score on a scale Standard Deviation 6.0	22.3 score on a scale Standard Deviation 6.2
Change From Baseline to Week 12 in Weekly DGSSD 4-symptom Composite Score (Nausea, Bloating, Early Satiety, Abdominal Pain) Change from Baseline to Week 12	-5.4 score on a scale Standard Deviation 8.1	-7.7 score on a scale Standard Deviation 7.8	-7.5 score on a scale Standard Deviation 7.4	-8.9 score on a scale Standard Deviation 8.3

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

GE was measured via the GEBT and was reported as a time to half (t1/2) of the theoretical total GE. GEBT is a non-radioactive stable isotope breath test intended for measurement of GE of solids in participants. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg n=98 Participants Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg n=109 Participants Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg n=81 Participants Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time Baseline	127.1 minutes Standard Deviation 36.5	126.8 minutes Standard Deviation 37.6	128.6 minutes Standard Deviation 35.9	133.6 minutes Standard Deviation 35.4
Change From Baseline to Week 12 for Gastric Emptying (GE) as Measured by the Gastric Emptying Breath Test (GEBT) Half-time Change from Baseline to Week 12	0.0 minutes Standard Deviation 38.5	-12.7 minutes Standard Deviation 38.1	-12.8 minutes Standard Deviation 36.5	-13.6 minutes Standard Deviation 40.5

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Relamorelin 10 μg

Serious events: 7 serious events

Other events: 21 other events

Deaths: 0 deaths

Relamorelin 30 μg

Serious events: 10 serious events

Other events: 30 other events

Deaths: 0 deaths

Relamorelin 100 μg

Serious events: 6 serious events

Other events: 28 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=104 participants at risk Placebo-matching relamorelin was administered subcutaneously (SC) by injection twice daily (BID) for 12 weeks.	Relamorelin 10 μg n=98 participants at risk Relamorelin 10 microgram (μg) was administered SC by injection BID for 12 weeks.	Relamorelin 30 μg n=109 participants at risk Relamorelin 30 μg was administered SC by injection BID for 12 weeks.	Relamorelin 100 μg n=82 participants at risk Relamorelin 100 μg was administered SC by injection BID for 12 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	4.1% 4/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	6.4% 7/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	7.3% 6/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Infections and infestations Urinary tract infection	6.7% 7/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	7.1% 7/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	7.3% 8/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	7.3% 6/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Investigations Blood glucose increased	0.96% 1/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	3.1% 3/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	3.7% 4/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	7.3% 6/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	1.9% 2/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	5.1% 5/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	9.2% 10/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	12.2% 10/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Nervous system disorders Dizziness	0.96% 1/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	0.00% 0/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	0.92% 1/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	6.1% 5/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.
Nervous system disorders Headache	2.9% 3/104 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	4.1% 4/98 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	5.5% 6/109 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.	2.4% 2/82 • Up to 98 days Safety set included all the participants who were randomized and received at least 1 dose of study treatment.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER