parallel randomized trial

NCT03985293

A 16-WEEK, PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TWICE DAILY PF-06882961 ADMINISTRATION IN ADULTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN OR DIET AND EXERCISE

Type 2 diabetes (adults)NCT03985293S001191

Design

Randomized: 412
Start year: 2020
Treatment: 16 weeks, follow-up 20 weeks
Countries: Bulgaria, Canada, Hungary, Republic of Korea, Poland, Slovakia, Taiwan, United States (97 sites)
Sponsor: Pfizer (industry)
Eligibility: age 18 to 75; HbA1c 7 to 10.5 percent; BMI 22.5 (Asia) or 24.5 to 45.4; metformin or diet and exercise

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo	metformin (91 percent) or diet and exercise; lifestyle: not reported	66	66	57
A2	Danuglipron 2.5 mg tablet twice daily Danuglipron 2.5 mg BID	metformin (91 percent) or diet and exercise; lifestyle: not reported	68	68	54
A3	Danuglipron 10 mg tablet twice daily Danuglipron 10 mg BID	metformin (91 percent) or diet and exercise; lifestyle: not reported	68	68	63
A4	Danuglipron 40 mg oral twice daily Danuglipron 40 mg BID	metformin (91 percent) or diet and exercise; lifestyle: not reported	71	71	57
A5	Danuglipron 80 mg oral twice daily Danuglipron 80 mg BID	metformin (91 percent) or diet and exercise; lifestyle: not reported	67	67	47
A6	Danuglipron 120 mg oral twice daily Danuglipron 120 mg BID	metformin (91 percent) or diet and exercise; lifestyle: not reported	72	71	38

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Placebo A1	Danuglipron 2.5 mg tablet twice daily A2	Danuglipron 10 mg tablet twice daily A3	Danuglipron 40 mg oral twice daily A4	Danuglipron 80 mg oral twice daily A5	Danuglipron 120 mg oral twice daily A6
age	mean (years)	57.9	58.9	58.1	59.6	58.4	58.8
age	sd (years)	10.27	9.30	9.43	8.58	9.18	9.43
asian	n	5	7	4	6	6	7
asian	percent	8	10	6	8	9	10
black	n	2	4	10	6	1	4
black	percent	3	6	15	8	1	6
bmi	mean (kg/m2)	32.5	32.5	33.0	32.3	32.9	33.3
bmi	sd (kg/m2)	5.08	5.17	5.34	5.25	5.06	5.70
diabetes duration	mean (years)	8.8	8.8	8.5	8.0	9.7	8.7
diabetes duration	sd (years)	6.90	6.31	6.85	5.82	6.20	7.89
female	n	33	30	33	37	32	37
female	percent	50	44	49	52	48	52
hba1c	mean (percent)	8.24	8.10	8.01	8.00	8.07	8.05
hba1c	sd (percent)	0.90	1.03	0.91	0.89	0.95	0.86
hispanic	n	24	22	17	24	23	18
hispanic	percent	36	32	25	34	34	25
metformin use	n	62	63	63	63	62	63
metformin use	percent	94	93	93	89	93	89
other race native hawaiian pacific islander	n	1	0	0	0	0	1
other race native hawaiian pacific islander	percent	2					1
weight	mean (kg)	90.1	90.9	92.3	90.2	91.3	93.1
weight	sd (kg)	17.54	20.13	16.44	18.74	16.64	17.95
white	n	57	57	53	58	59	59
white	percent	86	84	78	82	88	83

Analyses this trial contributes to

Results

139 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (22 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	change	-0.13 percent	-0.34 to 0.09	59	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A1	change	-0.02 percent	-0.22 to 0.19	52	hypothetical; modified itt; R0006095:Table 2
16	A2 vs A1	md	-0.35 percent	-0.65 to -0.06		treatment policy; modified itt; R0006095:Supplement eTable 7
16	A2	change	-0.48 percent	-0.70 to -0.26	54	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A2	change	-0.49 percent	-0.70 to -0.28	52	hypothetical; modified itt; R0006095:Table 2
16	A2 vs A1	md	-0.47 percent	-0.76 to -0.18		hypothetical; modified itt; R0006095:Table 2
16	A3	change	-0.91 percent	-1.11 to -0.70	65	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A3	change	-0.91 percent	-1.11 to -0.72	61	hypothetical; modified itt; R0006095:Table 2
16	A3 vs A1	md	-0.90 percent	-1.18 to -0.62		hypothetical; modified itt; R0006095:Table 2
16	A3 vs A1	md	-0.78 percent	-1.07 to -0.49		treatment policy; modified itt; R0006095:Supplement eTable 7
16	A4 vs A1	md	-0.85 percent	-1.14 to -0.56		treatment policy; modified itt; R0006095:Supplement eTable 7
16	A4	change	-1.03 percent	-1.23 to -0.83	55	hypothetical; modified itt; R0006095:Table 2
16	A4 vs A1	md	-1.01 percent	-1.30 to -0.73		hypothetical; modified itt; R0006095:Table 2
16	A4	change	-0.97 percent	-1.18 to -0.77	61	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A5	change	-0.68 percent	-0.89 to -0.47	58	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A5 vs A1	md	-0.94 percent	-1.24 to -0.65		hypothetical; modified itt; R0006095:Table 2
16	A5 vs A1	md	-0.55 percent	-0.85 to -0.26		treatment policy; modified itt; R0006095:Supplement eTable 7
16	A5	change	-0.96 percent	-1.18 to -0.74	46	hypothetical; modified itt; R0006095:Table 2
16	A6	change	-1.18 percent	-1.41 to -0.95	38	hypothetical; modified itt; R0006095:Table 2
16	A6	change	-0.96 percent	-1.17 to -0.74	54	treatment policy; modified itt; R0006095:Supplement eTable 7
16	A6 vs A1	md	-0.83 percent	-1.13 to -0.54		treatment policy; modified itt; R0006095:Supplement eTable 7
16	A6 vs A1	md	-1.16 percent	-1.47 to -0.86		hypothetical; modified itt; R0006095:Table 2

Body weight change in kilograms (diabetes) (11 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	change	-0.43 kg	-1.12 to 0.25	52	hypothetical; modified itt; R0006095:Table 2
16	A2	change	0.02 kg	-0.68 to 0.72	53	hypothetical; modified itt; R0006095:Table 2
16	A2 vs A1	md	0.45 kg	-0.50 to 1.41		hypothetical; modified itt; R0006095:Table 2
16	A3	change	-0.06 kg	-0.71 to 0.60	62	hypothetical; modified itt; R0006095:Table 2
16	A3 vs A1	md	0.38 kg	-0.54 to 1.30		hypothetical; modified itt; R0006095:Table 2
16	A4 vs A1	md	-0.73 kg	-1.66 to 0.20		hypothetical; modified itt; R0006095:Table 2
16	A4	change	-1.16 kg	-1.84 to -0.49	57	hypothetical; modified itt; R0006095:Table 2
16	A5	change	-2.48 kg	-3.20 to -1.75	46	hypothetical; modified itt; R0006095:Table 2
16	A5 vs A1	md	-2.04 kg	-3.01 to -1.07		hypothetical; modified itt; R0006095:Table 2
16	A6	change	-4.60 kg	-5.34 to -3.86	38	hypothetical; modified itt; R0006095:Table 2
16	A6 vs A1	md	-4.17 kg	-5.15 to -3.18		hypothetical; modified itt; R0006095:Table 2

HbA1c below 7 percent (11 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	responders			4 / 52	hypothetical; modified itt; R0006095:Results
16	A2	responders			16 / 52	hypothetical; modified itt; R0006095:Results
16	A2 vs A1	or	5.11	1.84 to 14.18		not stated; modified itt; registry:outcomes
16	A3 vs A1	or	16.85	6.18 to 45.93		not stated; modified itt; registry:outcomes
16	A3	responders			33 / 61	hypothetical; modified itt; R0006095:Results
16	A4	responders			32 / 55	hypothetical; modified itt; R0006095:Results
16	A4 vs A1	or	18.79	7.03 to 50.21		not stated; modified itt; registry:outcomes
16	A5	responders			30 / 46	hypothetical; modified itt; R0006095:Results
16	A5 vs A1	or	23.97	8.66 to 66.39		not stated; modified itt; registry:outcomes
16	A6	responders			23 / 38	hypothetical; modified itt; R0006095:Results
16	A6 vs A1	or	24.46	8.72 to 68.57		not stated; modified itt; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (24 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 66	not stated; safety; R0006095:Supplement eTable 1
A1	events	0 / 66	not stated; safety; R0006095:Supplement eTable 1
A1	events	0 / 66	not stated; safety; R0006095:Table 3
A1	events	0 / 66	not stated; safety; R0006095:Supplement eTable 1
A2	events	0 / 68	not stated; safety; R0006095:Supplement eTable 1
A2	events	1 / 68	not stated; safety; R0006095:Supplement eTable 1
A2	events	0 / 68	not stated; safety; R0006095:Supplement eTable 1
A2	events	1 / 68	not stated; safety; R0006095:Table 3
A3	events	1 / 68	not stated; safety; R0006095:Supplement eTable 1
A3	events	0 / 68	not stated; safety; R0006095:Supplement eTable 1
A3	events	0 / 68	not stated; safety; R0006095:Supplement eTable 1
A3	events	1 / 68	not stated; safety; R0006095:Table 3
A4	events	4 / 71	not stated; safety; R0006095:Table 3
A4	events	0 / 71	not stated; safety; R0006095:Supplement eTable 1
A4	events	2 / 71	not stated; safety; R0006095:Supplement eTable 1
A4	events	1 / 71	not stated; safety; R0006095:Supplement eTable 1
A5	events	0 / 67	not stated; safety; R0006095:Supplement eTable 1
A5	events	3 / 67	not stated; safety; R0006095:Supplement eTable 1
A5	events	2 / 67	not stated; safety; R0006095:Supplement eTable 1
A5	events	6 / 67	not stated; safety; R0006095:Table 3
A6	events	1 / 71	not stated; safety; R0006095:Supplement eTable 1
A6	events	3 / 71	not stated; safety; R0006095:Table 3
A6	events	0 / 71	not stated; safety; R0006095:Supplement eTable 1
A6	events	2 / 71	not stated; safety; R0006095:Supplement eTable 1

Systolic blood pressure change (11 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	change	-1.71 mmHg	-4.02 to 0.61	57	treatment policy; safety; R0006095:Supplement eTable 3
16	A2	change	-2.79 mmHg	-5.15 to -0.43	53	treatment policy; safety; R0006095:Supplement eTable 3
16	A2 vs A1	md	-1.08 mmHg	-4.14 to 1.98		treatment policy; safety; R0006095:Supplement eTable 3
16	A3	change	-2.85 mmHg	-5.05 to -0.64	63	treatment policy; safety; R0006095:Supplement eTable 3
16	A3 vs A1	md	-1.14 mmHg	-4.08 to 1.80		treatment policy; safety; R0006095:Supplement eTable 3
16	A4	change	-3.43 mmHg	-5.69 to -1.16	56	treatment policy; safety; R0006095:Supplement eTable 3
16	A4 vs A1	md	-1.72 mmHg	-4.71 to 1.27		treatment policy; safety; R0006095:Supplement eTable 3
16	A5	change	-6.65 mmHg	-9.07 to -4.23	46	treatment policy; safety; R0006095:Supplement eTable 3
16	A5 vs A1	md	-4.95 mmHg	-8.04 to -1.85		treatment policy; safety; R0006095:Supplement eTable 3
16	A6	change	-3.25 mmHg	-5.75 to -0.75	38	treatment policy; safety; R0006095:Supplement eTable 3
16	A6 vs A1	md	-1.54 mmHg	-4.73 to 1.65		treatment policy; safety; R0006095:Supplement eTable 3

Weight loss of 5 percent or more (6 lines; O11A)

Week	Arm	Statistic	Events / N	Detail
16	A1	responders	1 / 52	hypothetical; modified itt; R0006095:Results
16	A2	responders	3 / 53	hypothetical; modified itt; R0006095:Results
16	A3	responders	6 / 62	hypothetical; modified itt; R0006095:Results
16	A4	responders	10 / 57	hypothetical; modified itt; R0006095:Results
16	A5	responders	10 / 46	hypothetical; modified itt; R0006095:Results
16	A6	responders	18 / 38	hypothetical; modified itt; R0006095:Results

All cause mortality (6 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 66	not stated; safety; registry:adverse_events
A2	events	1 / 68	not stated; safety; registry:adverse_events
A3	events	0 / 68	not stated; safety; registry:adverse_events
A4	events	2 / 71	not stated; safety; registry:adverse_events
A5	events	0 / 67	not stated; safety; registry:adverse_events
A6	events	0 / 71	not stated; safety; registry:adverse_events

Serious adverse events (6 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	1 / 66	not stated; safety; R0006095:Table 3
A2	events	1 / 68	not stated; safety; R0006095:Table 3
A3	events	2 / 68	not stated; safety; R0006095:Table 3
A4	events	6 / 71	not stated; safety; R0006095:Table 3
A5	events	2 / 67	not stated; safety; R0006095:Table 3
A6	events	1 / 71	not stated; safety; R0006095:Table 3

Discontinuation due to adverse events (12 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 66	not stated; safety; R0006095:Table 3
A1	events	1 / 66	not stated; safety; R0006095:Table 3
A2	events	2 / 68	not stated; safety; R0006095:Table 3
A2	events	1 / 68	not stated; safety; R0006095:Table 3
A3	events	3 / 68	not stated; safety; R0006095:Table 3
A3	events	0 / 68	not stated; safety; R0006095:Table 3
A4	events	8 / 71	not stated; safety; R0006095:Table 3
A4	events	3 / 71	not stated; safety; R0006095:Table 3
A5	events	15 / 67	not stated; safety; R0006095:Table 3
A5	events	3 / 67	not stated; safety; R0006095:Table 3
A6	events	24 / 71	not stated; safety; R0006095:Table 3
A6	events	4 / 71	not stated; safety; R0006095:Table 3

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	2 / 66	not stated; safety; R0006095:Table 3
A2	events	5 / 68	not stated; safety; R0006095:Table 3
A3	events	5 / 68	not stated; safety; R0006095:Table 3
A4	events	11 / 71	not stated; safety; R0006095:Table 3
A5	events	22 / 67	not stated; safety; R0006095:Table 3
A6	events	23 / 71	not stated; safety; R0006095:Table 3

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 66	not stated; safety; R0006095:Table 3
A2	events	0 / 68	not stated; safety; R0006095:Table 3
A3	events	1 / 68	not stated; safety; R0006095:Table 3
A4	events	5 / 71	not stated; safety; R0006095:Table 3
A5	events	11 / 67	not stated; safety; R0006095:Table 3
A6	events	18 / 71	not stated; safety; R0006095:Table 3

Diarrhea (6 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	2 / 66	not stated; safety; R0006095:Table 3
A2	events	3 / 68	not stated; safety; R0006095:Table 3
A3	events	4 / 68	not stated; safety; R0006095:Table 3
A4	events	8 / 71	not stated; safety; R0006095:Table 3
A5	events	12 / 67	not stated; safety; R0006095:Table 3
A6	events	7 / 71	not stated; safety; R0006095:Table 3

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 66	not stated; safety; R0006095:Results
A2	events	0 / 68	not stated; safety; R0006095:Results
A3	events	0 / 68	not stated; safety; R0006095:Results
A4	events	0 / 71	not stated; safety; R0006095:Results
A5	events	1 / 67	not stated; safety; R0006095:Results
A6	events	0 / 71	not stated; safety; R0006095:Results

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 66	not stated; safety; R0006095:Results
A2	events	0 / 68	not stated; safety; R0006095:Results
A3	events	0 / 68	not stated; safety; R0006095:Results
A4	events	0 / 71	not stated; safety; R0006095:Results
A5	events	0 / 67	not stated; safety; R0006095:Results
A6	events	0 / 71	not stated; safety; R0006095:Results