A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Efficacy, Safety and Tolerability of NKTR-118 in Patients with Opioid-Induced Constipation (OIC)

INTERVENTION: Product Code: NKTR‐118 Pharmaceutical Form: Oral solution Current Sponsor code: NKTR‐118 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use Product Code: NKTR‐118 Pharmaceutical Form: Oral solution Current Sponsor code: NKTR‐118 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use Product Code: NKTR‐118 Pharmaceutical Form: Oral solution Current Sponsor code: NKTR‐118 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use Product Code: NKTR‐118 Pharmaceutical Form: Oral solution Current Sponsor code: NKTR‐118 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Oral solution Route of administration of the placebo: Oral use CONDITION: Opioid induced constipation PRIMARY OUTCOME: Main Objective: Objectives:; Primary Objective:; To evaluate the efficacy of NKTR‐118 at various dose levels, with efficacy defined as the change in the number of spontaneous bowel movements (SBMs) per week from baseline. The primary endpoint is the change from baseline in SBMs/week averaged throughout the treatment period, defined as SBMs/week for the overall treatment period minus baseline SBMs/week.; Primary end point(s): Primary Endpoint:; Change from baseline in SBMs/week averaged throughout the treatment period; this is defined to be SBMs/week for the overall treatment period minus baseline SBMs/week. SBM is defined as a bowel movement without the use of laxatives in the previous 24 hour. Secondary Objective: Secondary Objectives:; • To evaluate safety and tolerability of NKTR‐118, thereby enabling the identification of an effective dose that preserves opioid‐conferred analgesia; • Delineate dose‐response for NKTR‐118 across a range of underlying opioid doses, with response defined as the change in SBMs per week from baseline; • Characterize the pharmacokinetics (PK) of NKTR‐118 in patients; INCLUSION CRITERIA: 1. 18 years of age or older, male or female Female patients must be of non‐childbearing potential OR if they are of child‐bearing potential have a negative screening pregnancy test with a commitment to practice effective contraception throughout the duration of the study, including the Follow‐Up Period. Females who have had a surgical hysterectomy and/or bilateral oophorectomy, or are post‐menopausal and have not had a menstrual cycle for 12 consecutive months, are not considered to be of child‐bearing potential. Effective contraception will be defined as either 1) complete sexual abstinence; 2) double barrier methods of birth control such as female diaphragm with spermicidal jelly AND male condom, 3) an intrauterine device (IUD) AND single barrier method of contraception; 4) use of an oral topical contraceptive combined with a barrier method of birth control. Male patients must also practice effective contraception as defined above (i.e., they and their