Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects

Danto, Spencer I.; Shojaee, Negin; Singh, Ravi Shankar P.; Li, Cheryl; Gilbert, Steven A.; Manukyan, Zorayr; Kilty, Iain

doi:10.1186/s13075-019-2008-6

Table 2 Study 2 (MAD) TEAEs. All causalities (treatment-related)

From: Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects

	Placebo^a	PF-06650833 dose group
	Placebo^a	IR 25 mg BID	IR 100 mg BID	IR 250 mg BID	IR 750 mg BID	IR 1000 mg QID	IR 330 mg TID	MR 300 mg QD
Subjects evaluable for AEs	15	8	8	8	8	8	8	8
Subjects with AEs	6 (2)	3 (1)	4 (2)	3 (2)	5 (5)	7 (4)	3 (2)	4 (2)
Number of AEs	9 (3)	3 (1)	5 (2)	9 (7)	17 (13)	11 (6)	4 (2)	4 (2)
Number of subjects with AEs by system organ class and preferred term
Blood and lymphatic system disorders	0	0	0	0	0	1 (1)	0	0
Neutropenia	0	0	0	0	0	1 (1)	0	0
Ear and labyrinth disorders	0	0	0	0	0	1 (0)	0	0
Hypoacusis	0	0	0	0	0	1 (0)	0	0
Eye disorders	1 (0)	0	0	0	0	1 (0)	0	0
Conjunctival hyperemia	1 (0)	0	0	0	0	0	0	0
Conjunctival irritation	0	0	0	0	0	1 (0)	0	0
Gastrointestinal disorders	1 (0)	1 (0)	2 (2)	2 (2)	1 (1)	2 (2)	0	0
Abdominal discomfort	1 (0)	0	0	0	0	0	0	0
Abdominal pain upper	0	0	2 (2)	0	1 (1)	0	0	0
Diarrhea	0	0	0	0	0	1 (1)	0	0
Feces hard	0	1 (0)	0	0	0	0	0	0
Feces soft	0	0	0	0	1 (0)	0	0	0
Flatulence	0	0	0	0	0	1 (1)	0	0
Gastroesophageal reflux disease	0	0	0	0	1 (1)	0	0	0
Nausea	0	0	0	2 (2)	1 (1)	0	0	0
Vomiting	0	0	0	0	1 (1)	0	0	0
General disorders and administration site conditions	0	0	0	1 (1)	1 (1)	1 (1)	1 (1)	0
Asthenia	0	0	0	1 (1)	0	0	0	0
Fatigue	0	0	0	0	1 (1)	0	0	0
Feeling abnormal	0	0	0	0	0	0	1 (1)	0
Feeling hot	0	0	0	0	0	1 (1)	0	0
Infections and infestations	1 (1)	0	1 (0)	0	1 (1)	0	0	1 (0)
Folliculitis	0	0	0	0	1 (1)	0	0	0
Hordeolum	0	0	0	0	0	0	0	1 (0)
Upper respiratory tract infection	1 (1)	0	1 (0)	0	0	0	0	0
Injury, poisoning, and procedural complications	1 (0)	0	0	1 (0)	0	0	0	0
Arthropod bite	1 (0)	0	0	1 (0)	0	0	0	0
Metabolism and nutrition disorders	0	0	0	0	1 (1)	0	0	0
Decreased appetite	0	0	0	0	1 (1)	0	0	0
Musculoskeletal and connective tissue disorders	0	1 (0)	1 (0)	0	1 (0)	1 (0)	0	0
Back pain	0	1 (0)	0	0	0	0	0	0
Muscle spasms	0	0	0	0	1 (0)	1 (0)	0	0
Neck pain	0	0	1 (0)	0	0	0	0	0
Nervous system disorders	1 (0)	1 (1)	0	2 (2)	4 (4)	3 (2)	0	0
Dizziness	0	0	0	1 (1)	0	0	0	0
Headache	1 (0)	1 (1)	0	1 (1)	4 (4)	2 (2)	0	0
Presyncope	0	0	0	0	0	1 (0)	0	0
Somnolence	0	0	0	1 (1)	0	0	0	0
Psychiatric disorders	0	0	1 (0)	0	1 (1)	0	0	0
Anxiety	0	0	0	0	1 (1)	0	0	0
Insomnia	0	0	1 (0)	0	0	0	0	0
Renal and urinary disorders	0	0	0	0	1 (0)	0	1 (0)	1 (1)
Nocturia	0	0	0	0	1 (0)	0	0	0
Polyuria	0	0	0	0	0	0	1 (0)	1 (1)
Respiratory, thoracic, and mediastinal disorders	1 (1)	0	0	0	2 (1)	0	1 (1)	0
Epistaxis	0	0	0	0	1 (0)	0	0	0
Nasal congestion	1 (1)	0	0	0	0	0	1 (1)	0
Oropharyngeal pain	0	0	0	0	1 (1)	0	0	0
Skin and subcutaneous tissue disorders	3 (1)	0	0	2 (1)	0	1 (0)	1 (0)	2 (1)
Acne	1 (1)	0	0	1 (1)	0	0	0	1 (1)
Aquagenic pruritus	0	0	0	0	0	1 (0)	0	0
Dermatitis contact	0	0	0	0	0	0	1 (0)	0
Dry skin	1 (0)	0	0	0	0	0	0	0
Ecchymosis	1 (0)	0	0	1 (0)	0	0	0	0
Skin irritation	0	0	0	0	0	0	0	1 (0)

Subjects were counted only once per treatment in each row. The table includes all data collected since the first dose of study drug
AE adverse event, BID twice daily, IR immediate-release, MAD multiple ascending doses, MR modified-release, QD once daily, QID four times per day, TEAE treatment-emergent AE, TID three times per day
^aRepresents placebo groups (IR placebo and MR placebo) in all cohorts

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